The interaction of carbachol and strophantin on the electrical and mechanical events in electrically driven strips of guinea pig left atria.
We compared the electrophysiological and the mechanical actions of the cholinergic agonist carbachol (CARB) and the digitalis glycoside strophantin (STR) in a study on the electrically driven strips of guinea pig left atria. The respective control values for the resting membrane potential (RMP), action potential amplitude (APA), action potential duration at 20%, 50%, and 90% repolarization levels (APD20,50,90), and time to peak tension (TtPt) were of the order of 61.1 +/- 1.69 nmV, 104.64 +/- 1.28 mV, 28.5 +/- 1.22 msec, 51.0 +/- 1.51 msec, 106.91 +/- 3.81 msec, and 60.1 +/- 1.09 msec. Exposure to CARB (2 x 10(-7) M) rapidly reduced contractility, TtPt, APD, and APA to exceptionally lower levels within the initial 5 minutes and gradually caused a slight hyperpolarization in RMP. Strophantin (1 x 10(-7) M) caused contractility and RMP to increase slightly, APD and APA to reduce less markedly, but did not significantly affect TtPt. Under the influence of combined CARB/STR, the effect of CARB on the contraction amplitude (CA), TtPt, APD, and APA was attenuated and that on RMP was significantly potentiated (p < 0.05), whereas the effects of STR on CA, TtPt, APD, and APA were reversed (p < 0.05), and the effect on RMP was augmented. The action potential duration was less responsive to STR at all depolarization levels with respect to those of CARB and combined CARB/STR. Although the correlation between the time course of APD-20 and APD-90 for STR was poor, the correlation for CARB and combined CARB/STR was highly significant (r > 0.95). The correlation between the effects of CARB on CA and APD-90 was high but poor for the effect of combined CARB/STR. Striking to note is that the rate of induction of contractile changes with CARB (d(delta)/dt = 1.39 +/- 0.05%/sec), and its washout was more rapid (p < 0.05) in comparison to the rate of changes in APD-90 (0.98 +/- 0.05%/sec). This result, however, was not observed with combined CARB/STR. From the results we concluded that CARB and STR act as antagonists when used in combination, with the exception that only the effect on RMP was additive, with asignificant discordance between the rates of induction of effects on CA and APD-90, with the former being more rapid.
Küçukhüseyin
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Department of Pharmacology, Cerrahpasa Medical Faculty, University of Istanbul, Cerrahpasa-Istanbul, Turkey. tahic@istanbul.edu.tr
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D013328:Strophanthins / Q000494:pharmacology*
D002316:Cardiotonic Agents; D018721:Muscarinic Agonists; D013328:Strophanthins; D002217:Carbachol