Back to Search
Start Over
Adenosine inhibits paraventricular pre-sympathetic neurons through ATP-dependent potassium channels.
- Source :
-
Journal of neurochemistry [J Neurochem] 2010 Apr; Vol. 113 (2), pp. 530-42. Date of Electronic Publication: 2010 Jan 25. - Publication Year :
- 2010
-
Abstract
- Adenosine produces cardiovascular depressor effects in various brain regions. However, the cellular mechanisms underlying these effects remain unclear. The pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) play an important role in regulating arterial blood pressure and sympathetic outflow through projections to the spinal cord and brainstem. In this study, we performed whole-cell patch-clamp recordings on retrogradely labeled PVN neurons projecting to the intermediolateral cell column of the spinal cord in rats. Adenosine (10-100 microM) decreased the firing activity in a concentration-dependent manner, with a marked hyperpolarization in 12 of 26 neurons tested. Blockade of A(1) receptors with the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or intracellular dialysis of guanosine 5'-O-(2-thodiphosphate) eliminated the inhibitory effect of adenosine on labeled PVN neurons. Immunocytochemical labeling revealed that A(1) receptors were expressed on spinally projecting PVN neurons. Also, blocking ATP-dependent K(+) (K(ATP)) channels with 100 microM glibenclamide or 200 microM tolbutamide, but not the G protein-coupled inwardly rectifying K(+) channels blocker tertiapin-Q, abolished the inhibitory effect of adenosine on the firing activity of PVN neurons. Furthermore, glibenclamide or tolbutamide significantly decreased the adenosine-induced outward currents in labeled neurons. The reversal potential of adenosine-induced currents was close to the K(+) equilibrium potential. In addition, adenosine decreased the frequency of both spontaneous and miniature glutamatergic excitatory post-synaptic currents and GABAergic inhibitory post-synaptic currents in labeled neurons, and these effects were also blocked by 8-cyclopentyl-1,3-dipropylxanthine. Collectively, our findings suggest that adenosine inhibits the excitability of PVN pre-sympathetic neurons through A(1) receptor-mediated opening of K(ATP) channels.
- Subjects :
- 6-Cyano-7-nitroquinoxaline-2,3-dione pharmacology
Action Potentials drug effects
Animals
Bicuculline pharmacology
Dose-Response Relationship, Drug
Excitatory Amino Acid Antagonists pharmacology
Excitatory Postsynaptic Potentials drug effects
GABA Antagonists pharmacology
Glyburide pharmacology
Guanosine Diphosphate analogs & derivatives
Guanosine Diphosphate pharmacology
In Vitro Techniques
Male
Membrane Potentials drug effects
Membrane Potentials physiology
Patch-Clamp Techniques methods
Potassium Channel Blockers pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A1 metabolism
Sodium Channel Blockers pharmacology
Tetrodotoxin pharmacology
Thionucleotides pharmacology
Tolbutamide pharmacology
Triazines pharmacology
Triazoles pharmacology
Xanthines pharmacology
Adenosine pharmacology
Analgesics pharmacology
KATP Channels physiology
Neurons drug effects
Paraventricular Hypothalamic Nucleus cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 113
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20096091
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2010.06618.x