Acetylcholine activates a glibenclamide-sensitive K+ current in cat atrial myocytes.
The preceding paper [Y. G. Wang and S. L. Lipsius, Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1313-H1321, 1995.] showed that when an atrial myocyte is treated with two consecutive exposures to acetylcholine (ACh) separated by a recovery interval, the second ACh exposure elicits a larger increase in K+ conductance than the first ACh exposure. In the present study a nystatin-perforated patch whole cell recording method was used to determine the mechanisms underlying the potentiating effect of ACh on ACh-induced K+ currents and the nature of the potentiated K+ current. The K+ current potentiated by the second ACh exposure was selectively abolished by 1) M1 muscarinic receptor block by 0.1 microM pirenzepine, 2) depletion of sarcoplasmic reticulum (SR) Ca2+ stores by 1 microM ryanodine or 10 mM caffeine, 3) intracellular dialysis with 10 mM ethylene glycolbis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), 4) omitting external Ca2+, 5) 50% external Na+, 6) inhibition of protein kinase C by 0.01 microM staurosporine or 0.1 microM calphostin C, or 7) inhibition of ATP-sensitive K+ channels with 10 microM glibenclamide (Glib). AFDX-116 (100 microM), an M2 muscarinic receptor antagonist, selectively abolished the conventional ACh-activated K+ current and revealed an ACh-activated Glib-sensitive K+ current. In addition, with K+ conductances blocked and zero external Ca2+, 10 microM ACh induced a small nonselective inward current carried by Na+.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
Y G
YG
Department of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Lipsius
S L
SL
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009281:Naphthalenes; D010890:Pirenzepine / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D019311:Staurosporine
D000470:Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D012964:Sodium; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D000109:Acetylcholine; D011188:Potassium; D005905:Glyburide; D002118:Calcium