抄録
Aiming at clarifying the physiological and pathophysiological roles of Na+-Ca2+ exchanger (NCX) in cardiac EC coupling, we studied the ventricular myocytes of homozygous mice over-expressing NCX1.1 (NCX1.1(Tg), Iwamoto et al., J. Pharmacol. Sci. 92 (2004) Suppl.). In ventricular myocytes of NCX1.1(Tg), the protein content of NCX and NCX currents were enhanced to two fold of those of wild type (wt). NCX1.1(Tg) displayed modest cardiac hypertrophy at 8-11 weeks of age (Iwamoto et al., 2004). The fractional shortening of single ventricular myocytes was not different between NCX1.1(Tg) and wt when stimulated at 0.33 Hz. However, in contrast to wt, NCX1.1(Tg) showed frequency-dependent reduction of shortening at frequencies higher than 0.5 Hz. Partial blockade of the forward mode NCX activity by replacing 50% of the extracellular Na+ by Li+ abolished the frequency-dependent contractile dysfunction. The severely impaired cardiac function of NCX1.1(Tg) may have been masked by compensatory mechanisms. We therefore measured the plasma norepinephrine level, and found it to be significantly higher in NCX1.1(Tg) than in wt. These results indicate that, in NCX1.1(Tg), the augmented forward mode NCX activity impairs the cardiac E-C coupling, which is masked by compensatory up-regulation of sympathetic tone that may be partly responsible for the cardiac hypertrophy observed in NCX1.1(Tg). [Jpn J Physiol 54 Suppl:S106 (2004)]
