Inositol trisphosphate enhances calcium release in skinned cardiac and skeletal muscle

Abstract

Experiments from other laboratories suggest that inositol trisphosphate (InsP3) may be involved in the excitation-contraction coupling (ECC) process of cardiac and skeletal muscle. Our results support this hypothesis. Studying fiber bundles (less than 200-microns diameter) from guinea pig papillary muscles skinned with saponin and mechanically skinned single fibers from frog semitendinosus muscle, we find that calcium-induced force oscillations (observed in solutions containing low ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid and pCa 7.0) are enhanced in magnitude and frequency by InsP3 at concentrations as low as 1 microM. InsP3 at 10 microM can often induce such oscillations in mechanically skinned frog skeletal muscle. In skinned cardiac fibers, InsP3 increases the magnitude of caffeine contractures at submaximal caffeine concentrations to a greater extent than at near-maximal caffeine concentrations. InsP3 (30 microM) has no effect on either the calcium sensitivity or maximal force generated by the contractile apparatus of skinned cardiac muscle. We conclude that InsP3 has no direct effect on the contractile machinery but that it can modulate ECC by enhancing the calcium-induced release of calcium from the sarcoplasmic reticulum, possibly from the same pool and through the same mechanism as caffeine.

Inositol phosphate production following α1‐adrenergic, muscarinic or electrical stimulation in isolated rat heart

“…cul-adrenergic, muscarinic and electrical stimulation. These observations and recent reports showing that addition of IP3 to sarcoplasmic reticulum induced a release of Ca*+ [12,26,27] suggest that IP3 might be involved in the excitation-contraction coupling in heart cells.…”

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

“…angiotensin II [131] or 5-hydroxytryptamine [124]). IP 3 does not alter myofilament Ca 2+ responsiveness [48]. Rather, the positive inotropic effect of IP 3 in atrial myocardium is mediated by enhanced Ca 2+ release from the SR.…”

“…However, there are reports suggesting that IP 3 Rs are also expressed in other cardiac regions/cell types, such as papillary muscle [48,159].It has also been proposed that IP 3 Rs are functional in nodal cells within the developing atria. Isolation of atrial cells from E14.5 mouse embryos revealed a minor population of spontaneously active myocytes (presumed to be pacemaking cells).…”

“…Indeed, the notion that IP 3 mediates Ca 2+ release in the heart is not new, and has been established by studies spanning the last two decades. The very earliest studies on cardiac IP 3 signaling found evidence for functional IP 3 Rs capable of releasing Ca 2+ from the SR [47][48][49][50][51]. However, compared with Ca 2+ -induced Ca 2+ release through RyRs, though, the IP 3 -induced Ca 2+ release was slow and small.…”

Right atrial dilatation increases inositol‐(1,4,5)trisphosphate accumulation Implications for the control of atrial natriuretic peptide release

“…Ins(l,4,5)P2 has been reported to be active [15], inactive [16] and weak [17] in releasing calcium from cardiac sarcoplasmic reticulum. Therefore its role in the heart is unclear.…”