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J Physiol Volume 545, Number 2, 375-388, December 1, 2002 DOI: 10.1113/jphysiol.2002.028605
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Journal of Physiology (2002), 545.2, pp. 375-388
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.028605

beta-Adrenergic and muscarinic agonists modulate inactivation of L-type Ca2+ channel currents in guinea-pig ventricular myocytes

Ian Findlay

CNRS UMR 6542, Faculté des Sciences, Université de Tours, France

The objective of this study was to examine the effects of isoproterenol (isoprenaline) and carbachol upon voltage-dependent inactivation of L-type Ca2+ current (ICa,L). ICa,L was recorded in guinea-pig isolated ventricular myocytes in the presence and absence of extracellular Ca2+ to separate total inactivation and voltage-dependent inactivation. In the presence of Ca2+, isoproterenol and carbachol had 'competitive' effects upon the relationships between membrane voltage and ICa,L amplitude and inactivation. Neither agonist had a marked effect upon the decay of inward ICa,L carried by Ca2+. In the absence of Ca2+, isoproterenol severely reduced and slowed ICa,L inactivation; this effect was reversed by carbachol. Under control conditions decay was dominated by fast inactivation. Isoproterenol reduced fast-inactivating and increased time-independent currents in a dose-dependent manner. These effects were counteracted by carbachol. There was a reciprocal relationship between the amplitude of fast-inactivating and time-independent currents with agonist stimulation. It is concluded that agonist modulation of rapid voltage-dependent inactivation of L-type Ca2+ channels involves an 'on-off' switch.



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