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Effect of Forskolin and Acetyicholine on Calcium Current in Single Isolated Cardiac Myocytes

Abstract : The effect of extracellular and intracellular application of forskolin on the voltage-sensitive calcium current, lCa, was studied in myocytes isolated from frog ventricle. Myocytes were isolated by enzymatic dissociation, and ICa was measured using the whole-cell configuration of the patch clamp technique modified to permit intracellular perfusion of various substances. Intracellular perfusion with forskolin (0.1 to 10 µM) had a negligible effect on ICa. ICa was increased 15±13% (mean ± SE; N = 5). In contrast, superfusion of the cell with forskolin increased ICa significantly. The EC50 for the forskolin effect was 0.4 µM. A maximal 4.5-fold increase in ICa occurred with 3 µM forskolin. This is somewhat less than the maximal response to Isoprenaline seen in this same series of experiments. The effects of forskolin, isoprenaline, and intracellular cAMP were not additive. In contrast, the effects of isoprenaline or intracellular cAMP and calcium channel agonists, such as Sandoz (+)202-791, were additive. This supports the hypothesis that the positive inotropic effects of forskolin are at least partly mediated by an increase in intracellular cAMP and a stimulation of ICa. The effects of forskolin were antagonized by acetylcholine (1 µM) or intracellular perfusion with cGMP. Acetylcholine on the average decreased forskolin-stimulated ICa 57±1.1% (N = 17). The relevance of these results to the suggestion that acetylcholine acts by mechanisms other than inhibition of adenylate cyclase is discussed.
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Contributor : RODOLPHE FISCHMEISTER Connect in order to contact the contributor
Submitted on : Thursday, March 24, 2022 - 4:33:17 PM
Last modification on : Thursday, March 31, 2022 - 3:59:19 AM
Long-term archiving on: : Saturday, June 25, 2022 - 7:44:17 PM


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  • HAL Id : hal-03618938, version 1
  • PUBMED : 2446114


H Hartzell, R Fischmeister. Effect of Forskolin and Acetyicholine on Calcium Current in Single Isolated Cardiac Myocytes. Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 1987, 32 (5), pp.639-45. ⟨hal-03618938⟩



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