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.
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 myocytes using Indo-1. Macroscopic membrane currents were simultaneously recorded using the whole-cell patch-clamp technique.


RESULTS
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.


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.
Evans
A M
AM
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, UK.
Cannell
M B
MB
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007211:Indoles; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005456:Fluorescent Dyes; D007211:Indoles; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D014700:Verapamil; C048960:indo-1; D002118:Calcium