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IP3 receptor-dependent Ca2+ release modulates excitation-contraction coupling in rabbit ventricular myocytes.

Domeier TL, Zima AV, Maxwell JT, Huke S, Mignery GA, Blatter LA
Am J Physiol Heart Circ Physiol. 2008 294 (2): H596-604

PMID: 18055509 · DOI:10.1152/ajpheart.01155.2007

Inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R)-dependent Ca(2+) signaling exerts positive inotropic, but also arrhythmogenic, effects on excitation-contraction coupling (ECC) in the atrial myocardium. The role of IP(3)R-dependent sarcoplasmic reticulum (SR) Ca(2+) release in ECC in the ventricular myocardium remains controversial. Here we investigated the role of this signaling pathway during ECC in isolated rabbit ventricular myocytes. Immunoblotting of proteins from ventricular myocytes showed expression of both type 2 and type 3 IP(3)R at levels approximately 3.5-fold less than in atrial myocytes. In permeabilized myocytes, direct application of IP(3) (10 microM) produced a transient 21% increase in the frequency of Ca(2+) sparks (P < 0.05). This increase was accompanied by a 13% decrease in spark amplitude (P < 0.05) and a 7% decrease in SR Ca(2+) load (P < 0.05) and was inhibited by IP(3)R antagonists 2-aminoethoxydiphenylborate (2-APB; 20 microM) and heparin (0.5 mg/ml). In intact myocytes endothelin-1 (100 nM) was used to stimulate IP(3) production and caused a 38% (P < 0.05) increase in the amplitude of action potential-induced (0.5 Hz, field stimulation) Ca(2+) transients. This effect was abolished by the IP(3)R antagonist 2-APB (2 microM) or by using adenoviral expression of an IP(3) affinity trap that buffers cellular IP(3). Together, these data suggest that in rabbit ventricular myocytes IP(3)R-dependent Ca(2+) release has positive inotropic effects on ECC by facilitating Ca(2+) release through ryanodine receptor clusters.

MeSH Terms (19)

Adenoviridae Animals Blotting, Western Calcium Calcium Signaling Cats Cell Separation Heart Ventricles Inositol 1,4,5-Trisphosphate Receptors In Vitro Techniques Lipid Bilayers Microscopy, Confocal Myocardial Contraction Myocytes, Cardiac Rabbits RNA Ryanodine Receptor Calcium Release Channel Sarcoplasmic Reticulum Signal Transduction

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