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Magnetogenetics was developed to remotely control genetically targeted neurons. A variant of magnetogenetics uses magnetic fields to activate transient receptor potential vanilloid (TRPV) channels when coupled with ferritin. Stimulation with static or RF magnetic fields of neurons expressing these channels induces Ca 2+ transients and modulates behavior. However, the validity of ferritin-based magnetogenetics has been questioned due to controversies surrounding the underlying mechanisms and deficits in reproducibility. Here, we validated the magnetogenetic approach Ferritin-iron Redistribution to Ion Channels (FeRIC) using electrophysiological (Ephys) and imaging techniques. Previously, interference from RF stimulation rendered patch-clamp recordings inaccessible for magnetogenetics. We solved this limitation for FeRIC, and we studied the bioelectrical properties of neurons expressing TRPV4 (nonselective cation channel) and transmembrane member 16A (TMEM16A; chloride-permeable channel) coupled to ferritin (FeRIC channels) under RF stimulation. We used cultured neurons obtained from the rat hippocampus of either sex. We show that RF decreases the membrane resistance (Rm) and depolarizes the membrane potential in neurons expressing TRPV4 FeRIC RF does not directly trigger action potential firing but increases the neuronal basal spiking frequency. In neurons expressing TMEM16A FeRIC , RF decreases the Rm, hyperpolarizes the membrane potential, and decreases the spiking frequency. Additionally, we corroborated the previously described biochemical mechanism responsible for RF-induced activation of ferritin-coupled ion channels. We solved an enduring problem for ferritin-based magnetogenetics, obtaining direct Ephys evidence of RF-induced activation of ferritin-coupled ion channels. We found that RF does not yield instantaneous changes in neuronal membrane potentials. Instead, RF produces responses that are long-lasting and moderate, but effective in controlling the bioelectrical properties of neurons., Competing Interests: E.J.B and C.L. share ownership of a patent application (WO2016004281 A1 PCT/US2015/038948) relating to the use of Ferritin-iron Redistribution to Ion Channels for cell modulation and treatments. All other authors declare no competing financial interests., (Copyright © 2024 the authors.)

Purpose: There are 118 known elements. Nearly all of them have NMR active isotopes and at least 39 different nuclei have biological relevance. Despite this, most of today's MRI is based on only one nucleus- 1 H. To facilitate imaging all potential nuclei, we present a single transmit coil able to excite arbitrary nuclei in human-scale MRI., Theory and Methods: We present a completely new type of RF coil, the Any-nucleus Distributed Active Programmable Transmit Coil (ADAPT Coil), with fast switches integrated into the structure of the coil to allow it to operate at any relevant frequency. This coil eliminates the need for the expensive traditional RF amplifier by directly converting direct current (DC) power into RF magnetic fields with frequencies chosen by digital control signals sent to the switches. Semiconductor switch imperfections are overcome by segmenting the coil., Results: Circuit simulations demonstrated the effectiveness of the ADAPT Coil approach, and a 9 cm diameter surface ADAPT Coil was implemented. Using the ADAPT Coil, 1 H, 23 Na, 2 H, and 13 C phantom images were acquired, and 1 H and 23 Na ex vivo images were acquired. To excite different nuclei, only digital control signals were changed, which can be programmed in real time., Conclusion: The ADAPT Coil presents a low-cost, scalable, and efficient method for exciting arbitrary nuclei in human-scale MRI. This coil concept provides further opportunities for scaling, programmability, lowering coil costs, lowering dead-time, streamlining multinuclear MRI workflows, and enabling the study of dozens of biologically relevant nuclei., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

FeRIC (Ferritin iron Redistribution to Ion Channels) is a magnetogenetic technique that uses radiofrequency (RF) alternating magnetic fields to activate the transient receptor potential channels, TRPV1 and TRPV4, coupled to cellular ferritins. In cells expressing ferritin-tagged TRPV, RF stimulation increases the cytosolic Ca 2+ levels via a biochemical pathway. The interaction between RF and ferritin increases the free cytosolic iron levels that, in turn, trigger chemical reactions producing reactive oxygen species and oxidized lipids that activate the ferritin-tagged TRPV. In this pathway, it is expected that experimental factors that disturb the ferritin expression, the ferritin iron load, the TRPV functional expression, or the cellular redox state will impact the efficiency of RF in activating ferritin-tagged TRPV. Here, we examined several experimental factors that either enhance or abolish the RF control of ferritin-tagged TRPV. The findings may help optimize and establish reproducible magnetogenetic protocols., Competing Interests: C.L. shares ownership of a patent application (WO2016004281 A1 PCT/US2015/038948) relating to the use of FeRIC for cell modulation and treatments. All other authors declare that they have no competing interests., (© 2021 The Authors.)

Ethnopharmacological Relevance: Achillea millefolium L. (Asteraceae), known as yarrow (milenrama), is a plant used in Mexican traditional medicine for the treatment of hypertension, diabetes, and related diseases., Aim: To determine the vasorelaxant and antihypertensive effect of A. millefollium and to isolate the main bioactive antihypertensive agents., Materials and Methods: Organic (hexane, dichloromethane and methanol) and hydro-alcohol (Ethanol-H 2 O: 70:30) extracts obtained from flowers, leaves and stems were evaluated on isolated aorta rat rings with and without endothelium to determine their vasorelaxant effect. Hexane extract from flowers (HEAmF) was studied to evaluate its antihypertensive effect on spontaneously hypertensive rats (SHR). From HEAmF, bioactive compounds were obtained by bio-guided phytochemical separation through chromatography., Results: Organic extracts showed the best vasorelaxant activity. Hexane extract from flowers was the most potent and efficient ex vivo vasorelaxant agent, showing significant decrease of systolic and diastolic blood pressure in SHR (p < 0.05). Phytochemical separation of HEAmF yielded two epimeric sesquiterpene lactones: leucodin (1) and achillin (2), the major components of the extract. Both 1 and 2 showed similar vasorelaxant action ex vivo (p < 0.05), and their effects where modified by L-NAME (10 μM, nitric oxide synthase inhibitor), by ODQ (1 μM, soluble guanylyl cyclase inhibitor), and also relaxed the contraction induced by KCl (80 mM). Finally, 1 and 2 intragastric administration (50 mg/kg) decreased systolic and diastolic blood pressure in SHR., Conclusions: Achillea millefolium showed antihypertensive and vasorelaxant effects, due mainly to leucodin and achillin (epimers). Both compounds showed antihypertensive activity by vasorelaxation putatively by endothelium-dependent NO release and cGMP increase, as well as by calcium channels blockade., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Importance: Achillea millefolium L. (Asteraceae) is used for the treatment of respiratory diseases, diabetes, and hypertension., Aim: to explore its tracheal relaxant properties and clarify its functional mechanism of action on smooth muscle cells, which allow us to propose it as a potential anti-asthmatic drug., Material and Methods: organic and hydro-alcoholic extracts from A. millefolium were obtained by macerations, then their relaxing effect on ex vivo isolated rat trachea rings was determined. Most active extract (hexanic extract, EHAm) was studied to determine its functional mechanism of action using synergic, antagonist and inhibitor agents related with the contraction/relaxation process of the smooth muscle. Also, EHAm was subjected to bio-guided fractionation by open-column chromatography (on silica gel) using cyclohexane-EtOAc (80:20) in an isocratic way to isolate main bioactive compounds., Results: organic and hydro-alcoholic extracts showed relaxant effect in a concentration-response dependent manner, being EHAm the most active. The functional mechanism of action indicates that EHAm induced a non-competitive antagonism to the muscarinic receptors ; in addition, the NO/cGMP pathway is involved in the relaxation process of the tracheal smooth muscle. However, the most important mechanism of action showed by EHAm was related with the calcium channel blockade influx into the smooth muscle cells. On the other hand, epimeric sesquiterpene lactones leucodin (1) and achillin (2) were isolated and purified, which are responsible for the observed smooth muscle relaxant activity of the extract., Conclusion: hexanic extract of A. millefollium induced a significant relaxant effect on tracheal rat rings by calcium channel blockade and NO release., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. Author contributions to the paper were as follows: Extracts preparation, and leucodin and achillin isolation: L. A-D., M. H-M, F. Ch-S. Structural elucidation: G. N–V., I. L-R. Pharmacological evaluation: R. V-M., M. I–B., L. A-D., S. E-S. Identification and recollection of plant material: I. P-A. Study design: S. E-S. Manuscript preparation: all authors. Notes: The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

One approach to magnetogenetics uses radiofrequency (RF) waves to activate transient receptor potential channels (TRPV1 and TRPV4) that are coupled to cellular ferritins. The mechanisms underlying this effect are unclear and controversial. Theoretical calculations suggest that the heat produced by RF fields is likely orders of magnitude weaker than needed for channel activation. Using the FeRIC (Ferritin iron Redistribution to Ion Channels) system, we have uncovered a mechanism of activation of ferritin-tagged channels via a biochemical pathway initiated by RF disturbance of ferritin and mediated by ferritin-associated iron. We show that, in cells expressing TRPV FeRIC channels, RF increases the levels of the labile iron pool in a ferritin-dependent manner. Free iron participates in chemical reactions, producing reactive oxygen species and oxidized lipids that ultimately activate the TRPV FeRIC channels. This biochemical pathway predicts a similar RF-induced activation of other lipid-sensitive TRP channels and may guide future magnetogenetic designs., Competing Interests: Declaration of Interests C.L. shares ownership of a patent application (WO2016004281 A1 PCT/US2015/038948) relating to the use of FeRIC for cell modulation and treatments. All other authors declare that they have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Colon cancer cells, like other types of cancer cells, undergo the remodeling of the intracellular Ca 2+ homeostasis that contributes to cancer cell hallmarks including enhanced cell proliferation, migration, and survival. Colon cancer cells display enhanced store-operated Ca 2+ entry (SOCE) compared with their non-cancer counterparts. Colon cancer cells display an abnormal expression of SOCE molecular players including Orai1 and TRPC1 channels, and the stromal interacting molecule (STIM) 1 and 2. Interestingly, upregulation of Orai1 and TRPC1 channels and their contribution to SOCE are associated with cancer malignancy in colon cancer cells. In a specific cellular model of colon cancer, whereas in non-cancer colon cells SOCE is composed of the Ca 2+ release activated (CRAC) currents, in colon cancer cells SOCE is composed of CRAC- and cationic, non-selective store operated (SOC) currents. Former SOCs are mediated by TRPC1 channels. Moreover, colon cancer cells also display dysregulation of the expression of 1,4,5-triphosphate receptors (IP 3 R) that could contribute to the enhanced SOCE. Another important factor underlying the enhanced SOCE is the differential mitochondrial modulation of the CRAC and SOC currents in non-cancer and colon cancer cells. In colon cancer cells, mitochondria take up more Ca 2+ that prevent the Ca 2+ -dependent inactivation of the SOCs, leading to sustained Ca 2+ entry. Notably, the inhibition of SOCE in cancer colon cells abolishes their cancer hallmarks. Robust evidence has shown the efficiency of non-steroidal anti-inflammatory drugs (NSAIDs) and difluoromethylornithine (DFMO) to reverse the enhanced cell proliferation, migration, and apoptosis resistance of cancer cells. In colon cancer cells, both NSAIDs and DFMO decrease SOCE, but they target different molecular components of SOCE. NSAIDs decrease the Ca 2+ uptake by mitochondria, limiting their ability to prevent the Ca 2+ -dependent inactivation of the SOCs that underlie SOCE. On the other hand, DFMO inhibits the expression of TRPC1 channels in colon cancer cells, eliminating their contribution to SOCE. The identification of players of SOCE in colon cancer cells may help to better understand the remodeling of the Ca 2+ homeostasis in cancer. Importantly, the use of different pharmacological tools that target different SOCE molecular players in colon cancer cells may play a pivotal role in designing better chemoprevention strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Store-operated Ca 2+ entry (SOCE) is the most important Ca 2+ entry pathway in non-excitable cells. Colorectal cancer (CRC) shows decreased Ca 2+ store content and enhanced SOCE that correlate with cancer hallmarks and are associated to remodeling of store-operated channels (SOCs). Normal colonic cells display small, Ca 2+ -selective currents driven by Orai1 channels. In contrast, CRC cells display larger, non-selective currents driven by Orai1 and transient receptor potential canonical type 1 channels (TRPC1). Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), the limiting step in polyamine biosynthesis, strongly prevents CRC, particularly when combined with sulindac. We asked whether DFMO may reverse SOC remodeling in CRC. We found that CRC cells overexpress ODC and treatment with DFMO decreases cancer hallmarks including enhanced cell proliferation and apoptosis resistance. Consistently, DFMO enhances Ca 2+ store content and decreases SOCE in CRC cells. Moreover, DFMO abolish selectively the TRPC1-dependent component of SOCs characteristic of CRC cells and this effect is reversed by the polyamine putrescine. Combination of DFMO and sulindac inhibit both SOC components and abolish SOCE in CRC cells. Finally, DFMO treatment inhibits expression of TRPC1 and stromal interaction protein 1 (STIM1) in CRC cells. These results suggest that polyamines contribute to Ca 2+ channel remodeling in CRC, and DFMO may prevent CRC by reversing channel remodeling.

Intracellular Ca 2+ is a pleiotropic second messenger involved in control of different cell and physiological functions including long-term processes such as cell proliferation, migration and survival. Agonist-induced Ca 2+ entry in most cells, especially in non-excitable cells including epithelial cells, is mediated by store-operated Ca 2+ entry (SOCE), a Ca 2+ entry pathway activated by agonist-induced release of Ca 2+ from intracellular stores in the endoplasmic reticulum (ER). This pathway is modulated also by mitochondria which, acting as Ca 2+ sinks, take up Ca 2+ , thus limiting Ca 2+ -dependent inactivation of Ca 2+ -release activated Ca 2+ channels (CRAC). Compelling evidence shows that SOCE is upregulated in a large variety of cancer cells and this change contribute to cancer hallmarks. Mechanisms for enhanced SOCE include changes in expression of members of the Orai, Stromal interaction molecule (STIM) and canonical transient receptor potential channel (TRPc) gene families. Tumor cell mitochondria may contribute to SOCE upregulation in cancer as well. Molecular players involved in enhancing mitochondrial Ca 2+ uptake are upregulated in tumor cells whereas negative modulators are repressed. Furthermore, mitochondrial potential, the driving force for mitochondrial Ca 2+ uptake, is enhanced in tumor cells due to the Warburg effect. Finally, SOCE in tumor cells may be sustained further by the gain of function of non-selective TRPC channels permeable to Na + that favour Ca 2+ exit from mitochondria in exchange for Na + , thus limiting Ca 2+ -dependent inactivation of Orai1 channels. Therefore, tumor cell mitochondria may efficiently contribute to enhance and sustain SOCE in cancer. Interestingly, this effect could be counterbalanced by selected non-steroidal anti-inflammatory drugs (NSAIDs) reported to prevent colorectal cancer and other forms of cancer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk tissues. We report that two heat-activated transient receptor potential (TRP) ion channels, TRPV1 and TRPV4, were present in neural crest cells during critical windows of heart and face development. TRPV1 antagonists protected against the development of hyperthermia-induced defects in chick embryos. Treatment with chemical agonists of TRPV1 or TRPV4 replicated hyperthermia-induced birth defects in chick and zebrafish embryos. To test whether transient TRPV channel permeability in neural crest cells was sufficient to induce these defects, we engineered iron-binding modifications to TRPV1 and TRPV4 that enabled remote and noninvasive activation of these channels in specific cellular locations and at specific developmental times in chick embryos with radio-frequency electromagnetic fields. Transient stimulation of radio frequency-controlled TRP channels in neural crest cells replicated fever-associated defects in developing chick embryos. Our data provide a previously undescribed mechanism for congenital defects, whereby hyperthermia activates ion channels that negatively affect fetal development., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Tumor cells undergo a critical remodeling of intracellular Ca 2+ homeostasis that contribute to important cancer hallmarks. Store-operated Ca 2+ entry (SOCE), a Ca 2+ entry pathway modulated by mitochondria, is dramatically enhanced in colon cancer cells. In addition, most cancer cells display the Warburg effect, a metabolic switch from mitochondrial metabolism to glycolysis that provides survival advantages. Accordingly, we investigated mitochondria control of store-operated currents (SOCs) in two cell lines previously selected for representing human normal colonic cells and colon cancer cells. We found that, in normal cells, mitochondria are important for SOCs activity but they are unable to prevent current inactivation. In contrast, in colon cancer cells, mitochondria are dispensable for SOCs activation but are able to prevent the slow, Ca 2+ -dependent inactivation of SOCs. This effect is associated to increased ability of tumor cell mitochondria to take up Ca 2+ due to increased mitochondrial potential (ΔΨ) linked to the Warburg effect. Consistently with this view, selected non-steroidal anti-inflammatory drugs (NSAIDs) depolarize mitochondria, inhibit mitochondrial Ca 2+ uptake and promote SOC inactivation, leading to inhibition of both SOCE and cancer cell proliferation. Thus, mitochondria sustain store-operated currents in colon cancer cells but not in normal colonic cells and this effect is counteracted by selected NSAIDs providing a mechanism for cancer chemoprevention., Competing Interests: CONFLICTS OF INTEREST The authors disclose no conflicts of interest.

Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca 2+ entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca 2+ stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca 2+ -release activated Ca 2+ channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca 2+ stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity., Summary: Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca 2+ remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca 2+ entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca 2+ homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin metabolite salicylate and other NSAIDs inhibits tumor cell growth acting on SOCE, 3) evidences on the remodeling of intracellular Ca 2+ in cancer with a particular emphasis in SOCE, 4) the remodeling of SOCE and Ca 2+ store content in CRC and, finally, 5) the molecular basis of Ca 2+ remodeling in CRC. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ca(2+) entry pathways play important roles in control of many cellular functions, including long-term proliferation, migration and cell death. In recent years, it is becoming increasingly clear that, in some types of tumors, remodeling of Ca(2+) entry pathways could contribute to cancer hallmarks such as excessive proliferation, cell migration and invasion as well as resistance to cell death or survival. In this chapter we briefly review findings related to remodeling of Ca(2+) entry pathways in cancer with emphasis on the mechanisms that contribute to increased store-operated Ca(2+) entry (SOCE) and store-operated currents (SOCs) in colorectal cancer cells. Finally, since SOCE appears critically involved in colon tumorogenesis, the inhibition of SOCE by aspirin and other NSAIDs and its possible contribution to colon cancer chemoprevention is reviewed.

We have investigated the molecular basis of intracellular Ca(2+) handling in human colon carcinoma cells (HT29) versus normal human mucosa cells (NCM460) and its contribution to cancer features. We found that Ca(2+) stores in colon carcinoma cells are partially depleted relative to normal cells. However, resting Ca(2+) levels, agonist-induced Ca(2+) increases, store-operated Ca(2+) entry (SOCE), and store-operated currents (ISOC) are largely enhanced in tumor cells. Enhanced SOCE and depleted Ca(2+) stores correlate with increased cell proliferation, invasion, and survival characteristic of tumor cells. Normal mucosa cells displayed small, inward Ca(2+) release-activated Ca(2+) currents (ICRAC) mediated by ORAI1. In contrast, colon carcinoma cells showed mixed currents composed of enhanced ICRAC plus a nonselective ISOC mediated by TRPC1. Tumor cells display increased expression of TRPC1, ORAI1, ORAI2, ORAI3, and STIM1. In contrast, STIM2 protein was nearly depleted in tumor cells. Silencing data suggest that enhanced ORAI1 and TRPC1 contribute to enhanced SOCE and differential store-operated currents in tumor cells, whereas ORAI2 and -3 are seemingly less important. In addition, STIM2 knockdown decreases SOCE and Ca(2+) store content in normal cells while promoting apoptosis resistance. These data suggest that loss of STIM2 may underlie Ca(2+) store depletion and apoptosis resistance in tumor cells. We conclude that a reciprocal shift in TRPC1 and STIM2 contributes to Ca(2+) remodeling and tumor features in colon cancer., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Vascular smooth muscle cells undergo phenotypic switches after damage which may contribute to proliferative disorders of the vessel wall. This process has been related to remodeling of Ca(2+) channels. We have tested the ability of cultured human coronary artery smooth muscle cells (hCASMCs) to return from a proliferative to a quiescent behavior and the contribution of intracellular Ca(2+) remodeling to the process. We found that cultured, early passage hCASMCs showed a high proliferation rate, sustained increases in cytosolic [Ca(2+)] in response to angiotensin II, residual voltage-operated Ca(2+) entry, increased Stim1 and enhanced store-operated currents. Non-steroidal anti-inflammatory drugs inhibited store-operated Ca(2+) entry and abolished cell proliferation in a mitochondria-dependent manner. After a few passages, hCASMCs turned to a quiescent phenotype characterized by lack of proliferation, oscillatory Ca(2+) response to angiotensin II, increased Ca(2+) store content, enhanced voltage-operated Ca(2+) entry and Cav1.2 expression, and decreases in Stim1, store-operated current and store-operated Ca(2+) entry. We conclude that proliferating hCASMCs return to quiescence and this switch is associated to a remodeling of Ca(2+) channels and their control by subcellular organelles, thus providing a window of opportunity for targeting phenotype-specific Ca(2+) channels involved in proliferation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Nicotine, the main addictive substance in tobacco, interacts with muscle and neuronal nicotinic acetylcholine receptors (nAChRs) that are also localized in astrocytes. We studied electrical effects elicited by nicotine in cultured astrocytes from the CA1 area of the rat hippocampus. Nicotine elicited different types of responses: sustained inward currents, decaying inward currents, and biphasic responses (an outward, followed by an inward current). Nicotine showed two opposite effects, an increase or a decrease of astrocyte membrane conductance, when voltage ramps were applied during sustained inward currents. The former was isolated by blocking K+ currents with Cs+ and was inhibited by mecamylamine. The latter was mimicked by tetraethylammonium ion, and was obtained in the presence of nAChR antagonists (mecamylamine, methyllycaconitine plus dihydro-beta-erythroidine). Thus, these results indicate that nicotine activates nAChRs and directly inhibits K+ currents in cultured astrocytes from the CA1 region of the rat hippocampus.