Regulation kinetics of Na super(+)-Ca super(2+) exchange current in guinea-pig ventricular myocytes

• Published in: The Journal of physiology Vol. 529; no. 3; pp. 611 - 623
• Main Authors: Fujioka, Yasutada, Hiroe, Koh, Matsuoka, Satoshi
• Format: Journal Article
• Language: English
• Published: 01.12.2000
• ISSN: 0022-3751

To investigate the regulation of native cardiac Na super(+)-Ca super(2+) exchange by cytoplasmic Na super(+) (Na super(+) sub(i)) and Ca super(2+) (Ca super(2+) sub(i)), we recorded the Na super(+)-Ca super(2+) exchange current (I sub(Na-Ca)) from inside-out 'macro patches' excised from intact guinea-pig ventricular cells. The half-maximal concentration (K sub(h)) of Ca super(2+) sub(i) required to induce an inward I sub(Na-Ca) was 7 mu M. The K sub(h) of Na super(+) sub(i) required to induce an outward I sub(Na-Ca) was 21 mM, and tended to decrease at the steady state of Na super(+)-dependent inactivation. The time constant ( tau ) of Na super(+)-dependent inactivation was similar to 1.5 s at 100 mM Na super(+) sub(i) and 1 mu m Ca super(2+) sub(i). The K sub(h) for Na super(+) sub(i) was 14 mM. Ca super(2+) sub(i) augmented the peak outward I sub(Na-Ca) (K sub(h) = 0.2 mu M) and attenuated Na super(+)-dependent inactivation (K sub(h) = 2.2 mu M). The outward I sub(Na-Ca) was activated by 5 mu m Ca super(2+) sub(i) with a half-time to reach steady state(t sub( one half )) of similar to 0.4 s. This activation was composed of two exponential processes. Deactivation of the current upon Ca super(2+) sub(i) removal also consisted of two exponential processes and had a t one half of similar to 0.5 s. A Na super(+)-Ca super(2+) exchange model, consisting of one consecutive 4Na super(+):1Ca super(2+) exchange cycle and two inactive states, well mimicked the experimental data with regard to ion dependencies and regulation kinetics. These data provide detailed information on the kinetics of the Na super(+) sub(i)- and Ca super(2+)-dependent regulation of native Na super(+)-Ca super(2+) exchange. They also indicate that the regulation kinetics operate faster in macro patches than in the giant membrane patch from cardiac 'blebs', or in Xenopus oocytes expressing a cloned exchanger (NCX1.1).