title: Na/Ca exchange: regulator of intracellular calcium and source of arrhythmias in the heart.
abstract: The major effect of Na/Ca exchange (NCX) on the systolic Ca transient is secondary to its effect on the Ca content of the sarcoplasmic reticulum (SR). SR Ca content is controlled by a mechanism in which an increase of SR Ca produces an increase in the amplitude of the systolic Ca transient. This, in turn, increases Ca efflux on NCX as well as decreasing entry on the L-type current resulting in a decrease of both cell and SR Ca content. This control mechanism also changes the response to other maneuvers that affect excitation-contraction coupling. For example, potentiating the opening of the SR Ca release channel (ryanodine receptor, RyR) with caffeine produces an immediate increase in the amplitude of the systolic Ca transient. However, this increases efflux of Ca from the cell on NCX and then decreases SR Ca content until a new steady state is reached. Changing the activity of NCX (by decreasing external Na) changes the level of SR Ca reached by this mechanism. If the cell and SR are overloaded with Ca then Ca waves appear during diastole. These waves activate the electrogenic NCX and thereby produce arrhythmogenic-delayed afterdepolarizations. A major challenge is how to remove this arrhythmogenic Ca release without compromising the normal systolic release. We have found that application of tetracaine to decrease RyR opening can abolish diastolic release while simultaneously potentiating the systolic release.
authors: Unit of Cardiac Physiology, University of Manchester, 3.18 Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK.
authors: L A
authors: LA
authors: Venetucci
authors: A W
authors: AW
authors: Trafford
authors: S C
authors: SC
authors: O'Neill
authors: D A
authors: DA
authors: Eisner
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium