| First Author | Larbig R | Year | 2010 |
| Journal | J Physiol | Volume | 588 |
| Issue | Pt 17 | Pages | 3267-76 |
| PubMed ID | 20643777 | Mgi Jnum | J:176755 |
| Mgi Id | MGI:5292610 | Doi | 10.1113/jphysiol.2010.187708 |
| Citation | Larbig R, et al. (2010) Activation of reverse Na+-Ca2+ exchange by the Na+ current augments the cardiac Ca2+ transient: evidence from NCX knockout mice. J Physiol 588(Pt 17):3267-76 |
| abstractText | The hypothesis that Na(+) influx during the action potential (AP) activates reverse Na(+)-Ca(2+) exchange (NCX) and subsequent entry of trigger Ca(2+) is controversial. We tested this hypothesis by monitoring intracellular Ca(2+) before and after selective inactivation of I(Na) prior to a simulated action potential in patch-clamped ventricular myocytes isolated from adult wild-type (WT) and NCX knockout (KO) mice. First, we inactivated I(Na) using a ramp prepulse to 45 mV. In WT cells, inactivation of I(Na) decreased the Ca(2+) transient amplitude by 51.1 +/- 4.6% (P < 0.001, n = 14) and reduced its maximum release flux by 53.0 +/- 4.6% (P < 0.001, n = 14). There was no effect on diastolic Ca(2+). In striking contrast, Ca(2+) transients in NCX KO cardiomyocytes were unaffected by the presence or absence of I(Na) (n = 8). We obtained similar results when measuring trigger Ca(2+) influx in myocytes with depleted sarcoplasmic reticulum. In WT cells, inactivation of I(Na) decreased trigger Ca(2+) influx by 37.8 +/- 6% and maximum rate of flux by 30.6 +/- 7.7% at 2.5 mm external Ca(2+) (P < 0.001 and P < 0.05, n = 9). This effect was again absent in the KO cells (n = 8). Second, exposure to 10 mum tetrodotoxin to block I(Na) also reduced the Ca(2+) transients in WT myocytes but not in NCX KO myocytes. We conclude that I(Na) and reverse NCX modulate Ca(2+) release in murine WT cardiomyocytes by augmenting the pool of Ca(2+) that triggers ryanodine receptors. This is an important mechanism for regulation of Ca(2+) release and contractility in murine heart. |
