Potassium channel blockers differentially affect carbachol and (-)-N6-phenylisopropyladenosine on guinea-pig atria.
1. The effect of three different potassium channel blockers (tetraethylammonium, TEA; 4-aminopyridine, 4-AP; and apamin) and of variations in the concentration of K+ and Ca2+ in the medium, have been studied on the responses of guinea-pig isolated atria to (-)-N6-phenylisopropyladenosine (R-PIA), a stable adenosine A1-receptor agonist, and to carbachol, a muscarinic agonist. R-PIA and carbachol showed the same negative inotropic effects over a similar range of concentrations (3-300 microM), both in spontaneously beating and in electrically driven atria. 2. TEA (0.1 to 20 mM) and 4-AP (0.3 to 3 mM), both antagonized the negative inotropic and chronotropic effects of carbachol in a concentration-dependent manner. In contrast, these compounds failed to inhibit the effects induced by R-PIA. Apamin, a specific blocker of a low conductance Ca2+-activated K+ channel, was ineffective in accordance with the absence of these channels in atrial tissue. 3. TEA (0.1 to 20mM) inhibited the negative inotropic effect of carbachol, but not that of R-PIA, in atria paced and depolarized by a high K+ medium (22 mM). In this preparation Na+ current is abolished and the contraction induced by noradrenaline and electrical stimulation is solely dependent on Ca2+ influx currents. 4. Stepwise addition of Ca2+ to a calcium-depleted perfusing medium of electrically driven atria, induced a positive inotropic effect which was inhibited by R-PIA. In contrast, carbachol had no effect. 5. In agreement with our previous study, the data suggest that R-PIA acts on isolated atria by inhibiting Ca2+ influx through L-channels.
De Biasi
M
M
Department of Pharmacology, University of Padua, Padova, Italy.
Froldi
G
G
Ragazzi
E
E
Pandolfo
L
L
Caparrotta
L
L
Fassina
G
G
D015761:4-Aminopyridine; D000241:Adenosine / Q000031:analogs & derivatives*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000631:Aminopyridines; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D010660:Phenylisopropyladenosine; D002217:Carbachol; D015761:4-Aminopyridine; D000241:Adenosine