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

• Published in: Cardiovascular research 1997-08, Vol.35 (2), p.294-302
• Main Authors: EVANS, A. M, CANNELL, M. B
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - physiology; Cardiovascular system; Cytosol - metabolism; Fluorescent Dyes; Guinea Pigs; Indoles; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardium - cytology; Myocardium - metabolism; Patch-Clamp Techniques; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Sarcoplasmic Reticulum - physiology; Sodium - metabolism; Sodium Channels - physiology; Sodium-Calcium Exchanger - metabolism; Verapamil - pharmacology
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/s0008-6363(97)00117-x

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. Cytosolic Ca2+ transients were recorded from enzymatically dissociated guinea-pig ventricular myocytes using Indo-1. Macroscopic membrane currents were simultaneously recorded using the whole-cell patch-clamp technique. At room temperature (22-25 degrees 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 microM), 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 degrees C and cAMP (10 microM) added to the pipette solution. 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.