Search

Ca2+ influx into excitable cells is a prerequisite for neurotransmitter release and regulated exocytosis. Within the group of ten cloned voltage-gated Ca2+ channels, the Cav2.3-containing E-type Ca2+ channels are involved in various physiological processes, such as neurotransmitter release and exocytosis together with other voltage-gated Ca2+ channels of the Cav1, Cav2 and Cav3 subfamily. However, E-type Ca2+ channels also exhibit several subunit-specific features, most of which still remain poorly understood. Cav2.3-containing R-type channels (here called‘E-type channels’) are also located in presynaptic terminals and interact with some synaptic vesicle proteins, the so-called SNARE proteins, although lacking the classical synprint interaction site. E-type channels trigger exocytosis and are also involved in long-term potentiation. Recently, it was shown that the interaction of Cav2.3 with the EF-hand motif containing protein EFHC1 is involved in the aetiology and pathogenesis of juvenile myoclonic epilepsy. [ABSTRACT FROM AUTHOR]

The article presents an abstract of a research study concerning the interrelation between insulin secretion and a1E-type voltage-gated calcium channels. It informs about a new peptide toxin SNX-482 which was found to be a potent blocker of R-Iike Ca2+ currents in HEK-293 cells transfected with a1E. It also discussed the effect of SNX-482 on the insulin release in the insulinoma cell line INS-1.

Voltage-gated Ca 2+ channels (VGCCs) are considered to play a key role in auditory perception and information processing within the murine inner ear and brainstem. In the past, Ca v 1.3 L-type VGCCs gathered most attention as their ablation causes congenital deafness. However, isolated patch-clamp investigation and localization studies repetitively suggested that Ca v 2.3 R-type VGCCs are also expressed in the cochlea and further components of the ascending auditory tract, pointing to a potential functional role of Ca v 2.3 in hearing physiology. Thus, we performed auditory profiling of Ca v 2.3 +/+ controls, heterozygous Ca v 2.3 +/- mice and Ca v 2.3 null mutants (Ca v 2.3 -/- ) using brainstem-evoked response audiometry. Interestingly, click-evoked auditory brainstem responses (ABRs) revealed increased hearing thresholds in Ca v 2.3 +/- mice from both genders, whereas no alterations were observed in Ca v 2.3 -/- mice. Similar observations were made for tone burst-related ABRs in both genders. However, Ca v 2.3 ablation seemed to prevent mutant mice from total hearing loss particularly in the higher frequency range (36-42 kHz). Amplitude growth function analysis revealed, i.a., significant reduction in ABR wave W I and W III amplitude in mutant animals. In addition, alterations in W I -W IV interwave interval were observed in female Ca v 2.3 +/- mice whereas absolute latencies remained unchanged. In summary, our results demonstrate that Ca v 2.3 VGCCs are mandatory for physiological auditory information processing in the ascending auditory tract., (© 2019 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Voltage-gated Ca(2+) channels regulate cardiac automaticity, rhythmicity and excitation-contraction coupling. Whereas L-type (Cav 1·2, Cav 1·3) and T-type (Cav 3·1, Cav 3·2) channels are widely accepted for their functional relevance in the heart, the role of Cav 2·3 Ca(2+) channels expressing R-type currents remains to be elucidated. We have investigated heart rate dynamics in control and Cav 2·3-deficient mice using implantable electrocardiogram radiotelemetry and pharmacological injection experiments. Autonomic block revealed that the intrinsic heart rate does not differ between both genotypes. Systemic administration of isoproterenol resulted in a significant reduction in interbeat interval in both genotypes. It remained unaffected after administering propranolol in Cav 2·3(-|-) mice. Heart rate from isolated hearts as well as atrioventricular conduction for both genotypes differed significantly. Additionally, we identified and analysed the developmental expression of two splice variants, i.e. Cav 2·3c and Cav 2·3e. Using patch clamp technology, R-type currents could be detected in isolated prenatal cardiomyocytes and be related to R-type Ca(2+) channels. Our results indicate that on the systemic level, the pharmacologically inducible heart rate range and heart rate reserve are impaired in Cav 2·3 (-|-) mice. In addition, experiments on Langendorff perfused hearts elucidate differences in basic properties between both genotypes. Thus, Cav 2·3 does not only contribute to the cardiac autonomous nervous system but also to intrinsic rhythm propagation., (Copyright © 2012 John Wiley & Sons, Ltd.)

Purpose: In order to record light-evoked responses from photoreceptor cells and the higher neuronal retinal network, the isolated vertebrate retina represents a sensitive tool for basic research of retinal function and for testing the toxicity of ocular therapeutics. In the past, this in vitro technique was optimized for frog and bovine retina; it should be transferred now to the isolated murine retina because the model could allow for functional testing of genes involved in retinal signalling using wild-type and gene-inactivated mice. Thus, alterations in the electroretinogram (ERG) may reveal differences in retinal information processing because of the inactivation of a specific gene., Methods: We used a superfused vertebrate retina assay to test bovine and murine retina., Results: In order to evaluate the sensitivity of the ERG recording technique from the isolated murine retina, we first determined the light intensity response and the stability of the a-wave amplitude during ERG recording, which did not differ between the species. However, testing the dihydropyridine sensitivity of the a-wave, we found that the murine a-wave was highly sensitive towards racemic isradipine (8-25 nM) but the bovine retina a-wave was not. A similar species-dependent difference was observed for mibefradil (10 muM)., Conclusion: Murine and bovine retina differ with respect to transretinal signalling. At the level of photoreceptor cells, the ERG/a-wave is modulated by isradipine-sensitive voltage-gated Ca(2+) channels, which trigger feedback signalling to photoreceptors.