Isoproterenol inhibits residual fast channel via stimulation of beta-adrenoceptors in guinea-pig ventricular muscle.
When perfused with high K+ (8.1 to 14.9 mM)-Tyrode's solution, the upstroke of action potentials in the isolated guinea-pig ventricular muscle is composed of two components and there are two separable peaks in the first derivative, i.e., Vmax, fast and Vmax, slow. The Vmax, fast was a measure of activation of the residual fast channel, while the Vmax, slow was that of the slow channel. Isoproterenol depressed Vmax, fast with increase in Vmax, slow, in a concentration-dependent manner (10(-8) to 10(-6) M). This depression of Vmax, fast was greater at more depolarized levels of membrane potential. Therefore, the isoproterenol-induced depression of Vmax, fast may be due to a negative shift of the curve relating Vmax, fast to the take-off potential (Em) (Vmax--Em relationship), along the voltage axis. The negative shift of Vmax--Em relationship by isoproterenol was also recognized in small preparations the size of which is well within the space constant. The negative shift was inhibited in the presence of beta-blockers (pindolol 1 microgram/ml or atenolol 10 micrograms/ml) but not by a calcium antagonist, 1-verapamil (1 microgram/ml). These results suggest that isoproterenol blocks sodium channels in the depolarized ventricular muscle via stimulation of the beta-adrenoceptors and that the depression of Vmax, fast is not mediated by the well-known effects of isoproterenol on Vmax, slow, i.e., increased influx of Ca2+ ions.
Hisatome
I
I
Kiyosue
T
T
Imanishi
S
S
Arita
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D010869:Pindolol / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D011943:Receptors, Adrenergic, beta; D010869:Pindolol; D014700:Verapamil; D007545:Isoproterenol; D011188:Potassium