Acetylcholine reverses isoproterenol-induced depression of Vmax in residual Na channel-dependent action potentials of guinea-pig cardiac muscles.
We examined effects of acetylcholine (ACh) on isoproterenol (ISP)-induced changes of the upstroke velocity of the action potential (Vmax) in isolated 13.5 mM K(+)-depolarized atrial muscles from guinea-pigs, using conventional glass microelectrode techniques. In some experiments, ventricular muscles were also used, for purposes of comparison. ISP (0.1 microM) decreased the fast component of Vmax (Vmax,fast) and increased the slow component of Vmax (Vmax, slow) of the atrial muscle, as has been noted in ventricular muscle. ACh (0.1 microM) reversed or antagonized these effects of ISP. However, in the presence of atropine (0.1 microM), the antagonism disappeared. In the presence of the Ca2+ channel blocker, D600 (1 microM), the depressant effect of ISP on the Vmax,fast was augmented while ACh exerted a much less restorative effect on the ISP-induced, depressed Vmax,fast. Similar findings were obtained in low (0.36 and 0.072 mM) Ca2+ media. To investigate the possible involvement of GTP-binding protein (Gi) on these ACh effects, we performed similar experiments using atrial muscles obtained from guinea pigs pre-treated with pertussis toxin (150 micrograms/kg) for 48 h. In these preparations, the depressant effect of ISP on the Vmax,fast remained unaffected, while the reversing effect of ACh on the ISP-induced depression of Vmax,fast either specifically diminished or disappeared. These results show that ACh antagonizes the ISP-induced Vmax changes via stimulation of muscarinic ACh receptors and that this effect is presumably mediated by Gi and modified by intracellular Ca2+. Clinical implications are discussed.
Cheng
Y N
YN
Department of Physiology, Medical College of Oita, Japan.
Aomine
M
M
Arita
M
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D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors*; D008297:Male; D008839:Microelectrodes; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D015222:Sodium Channels; D005711:Gallopamil; D007545:Isoproterenol; D000109:Acetylcholine; D011188:Potassium