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Muscarinic receptor-mediated increase of intracellular Na+-ion activity and force of contraction

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The aim of the present study was to determine the mechanism of the positive inotropic effect of carbachol on ventricular myocardium. Carbachol produced a concentration-dependent (0.1 to 300 μmol/l) increase in contraction force on the catecholamine-depleted papillary muscle of the guinea pig without affecting the normal action potential or the slow action potential evoked in 24 mmol/l K+. Since atropine prevented the inotropic effect of carbachol, muscarinic receptors were involved. Carbachol (300 μmol/l) produced an increase in intracellular Na+-ion-activity,a Na i , by about 3 mmol/l in the quiescent muscle, and the time course of thea Na i change corresponded with the development of the positive inotropic effect as determined in the stimulated preparation (0.2 Hz). The effect of carbachol on force of contraction and ona Na i was diminished by reducing [Ca2+]0. The positive inotropic effect of carbachol was dependent on repetitive activity and was markedly enhanced in the presence of dihydro-ouabain. The results are consistent with the hypothesis, that carbachol increases the Na+ permeability of the sarcolemma via muscarinic receptors, and enhances force of contraction by stimulating the Na+−Ca2+-exchange.

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Correspondence to Michael Korth.

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Korth, M., Kühlkamp, V. Muscarinic receptor-mediated increase of intracellular Na+-ion activity and force of contraction. Pflugers Arch. 403, 266–272 (1985).

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Key words

  • Muscarinic receptor
  • Carbachol
  • Positive inotropic effect
  • Intracellular Na+-ion-activity
  • Guinea-pig papillary muscle