title: Modulation of N-type Ca2+ currents by A1-adenosine receptor activation in male rat pelvic ganglion neurons.
abstract: Modulation of voltage-activated Ca2+ channels by adenosine was investigated in male rat major pelvic ganglion (MPG) neurons by using the whole-cell variant of the patch-clamp technique. Adenosine inhibited high voltage-activated (HVA) Ca2+ currents in a concentration-dependent manner with an EC50 of 313 nM and a maximal inhibition of 36%, respectively. Inhibition of HVA Ca2+ currents in adrenergic and cholinergic MPG neurons was similar. Adenosine did not modulate T-type Ca2+ channels present in adrenergic MPG neurons. Reverse transcription-polymerase chain reaction analysis indicated that MPG neurons express mRNAs encoding A1 and A2a receptors. Ca2+ current inhibition by adenosine was mimicked by N6-cyclopentyladenosine, an A1-selective agonist (EC50 = 63 nM) and prevented by 100 nM 8-cyclopentyl-1,3-dipropylxanthine, an A1-selective antagonist. Conversely, CGS 21680, an A2a-selective agonist, displayed a relatively low potency (EC50 = 2200 nM) for inhibiting Ca2+ currents. The action of adenosine was significantly attenuated by 2 mM guanosine-5'-thiodiphosphate or 500 ng/ml pertussis toxin. The voltage dependence of adenosine-induced current inhibition was evident by 1) a bell-shaped profile between the current inhibition and test potentials, 2) kinetic slowing in the presence of agonist, and 3) relief of the current inhibition by a conditioning prepulse to +80 mV. Finally, 1 microM omega-conotoxin GVIA occluded adenosine-induced current inhibition. Taken together, we concluded that adenosine inhibits N-type Ca2+ currents by activation of A1 receptors via a voltage-dependent and PTX-sensitive pathway in rat MPG neurons. Our data may explain how adenosine acts as an inhibitory modulator of ganglionic and neuromuscular transmission in the pelvic plexus.
authors.affiliation: Department of Physiology and Institute of Basic Medical Science, Yonsei University Wonju College of Medicine, Wonju, Kangwon-Do, Korea.
authors.forename: K S
authors.initials: KS
authors.lastname: Park
authors.forename: S W
authors.initials: SW
authors.lastname: Jeong
authors.forename: S K
authors.initials: SK
authors.lastname: Cha
authors.forename: B S
authors.initials: BS
authors.lastname: Lee
authors.forename: I D
authors.initials: ID
authors.lastname: Kong
authors.forename: S R
authors.initials: SR
authors.lastname: Ikeda
authors.forename: J W
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D017931:DNA Primers; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D037342:Pertussis Toxin; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D017931:DNA Primers; D058906:Purinergic P1 Receptor Agonists; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D020960:omega-Conotoxins; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium