Modulation of N-type Ca2+ currents by A1-adenosine receptor activation in male rat pelvic ganglion neurons

Kyu Sang Park, Seong Woo Jeong, Seung Kyu Cha, Boo Soo Lee, In Deok Kong, Stephen R. Ikeda, Joong Woo Lee

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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 μM ω-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.

Original languageEnglish
Pages (from-to)501-508
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume299
Issue number2
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Modulation of N-type Ca<sup>2+</sup> currents by A<sub>1</sub>-adenosine receptor activation in male rat pelvic ganglion neurons'. Together they form a unique fingerprint.

Cite this