A M Evans1, M B Cannell. 1. Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, UK.
Abstract
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.
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.
Authors: Robert Larbig; Natalia Torres; John H B Bridge; Joshua I Goldhaber; Kenneth D Philipson Journal: J Physiol Date: 2010-07-19 Impact factor: 5.182
Authors: David Baddeley; Isuru D Jayasinghe; Leo Lam; Sabrina Rossberger; Mark B Cannell; Christian Soeller Journal: Proc Natl Acad Sci U S A Date: 2009-12-15 Impact factor: 11.205