The functional role of ionic regulation of the NaS+/Ca2S+ exchanger assessed in transgenic mouse hearts

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Maxwell, Krista Dawn
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Sodium-calcium exchange is the principal mechanism for cellular Ca 2+ efflux following a cardiac contraction. On a beat-to-beat basis, the Na+/Ca2+ exchanger removes a similar quantity of Ca2+ from cardiac cells as that entering through L-type Ca2+ channels. As such, the Na+/Ca2+ exchanger plays a critical role in controlling cardiac contractility. To begin determining whether or not ionic regulation of the Na+/Ca 2+ exchanger is physiologically relevant, transgenic mice overexpressing either the wild-type canine cardiac exchanger, NCX1.1, or a deletion mutant in which ionic regulation has been nearly abolished, were examined. The initial characterization was carried out on 'Xenopus laevis' oocytes expressing these two different exchangers to define their regulatory properties. Since these Na+/Ca2+ exchangers originated from a cloned canine exchanger and were being expressed in a mouse model system, the native regulatory processes of both dog and mouse Na+/C 2+ exchangers were then examined to determine whether or not species differences existed. Using the giant excised patch clamp technique, ventricular myocytes isolated from each species were studied. (Abstract shortened by UMI.)