© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
The role of L-type Ca2+ current and Na+ current-stimulated Na/Ca exchange in triggering SR calcium release in guinea-pig cardiac ventricular myocytes
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK
* Corresponding author. Tel.: +44 (181) 725-5625; fax: +44 (181) 725-3581; e-mail: mcannell@sghms.ac.uk
Objective: This study examines the relative ability of sodium current (INa)-stimulated reverse mode Na/Ca exchange and the L-type calcium current (ICa) to trigger calcium-induced calcium release (CICR) in guinea-pig ventricular myocytes. Methods: Cytosolic Ca2+ transients were recorded from enzymatically dissociated guinea-pig ventricular mycocytes using Indo-1. Macroscopic membrane currents were simultaneously recorded using the whole-cell patch-clamp technique. Results: At room temperature (22–25°C) Ca2+ transients were associated with the activation of INa, ICa or INa plus ICa in combination. However, after ICa was blocked by verapamil (10 µM), no Ca2+ transient could be evoked by the activation of INa alone at either –40 or +5 mV. Similar results were obtained with 5 and 8 mM intracellular sodium, and when the temperature of the bathing solution was raised to 35°C and cAMP (10 µM) added to the pipette solution. Conclusions: From consideration of the relative magnitudes of the Ca2+ influx via ICa and Na/Ca exchange and thermodynamic considerations, we suggest that ICa is the major source of ‘trigger’ calcium for CICR (and cardiac contraction) under normal conditions. Although the Na/Ca exchanger was incapable of triggering CICR under the conditions of these experiments, we suggest that it may become more important when cytosolic Ca2+ is elevated, a condition which will also lead to decrease the amplitude of ICa.
KEYWORDS Calcium channel, L-type; Calcium transient; Sarcoplasmic reticulum; Indo-1; Na+/Ca2+ exchange; Excitation–contraction coupling; Guinea pig, ventricular myocytes
1 Present address: University Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, UK.
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