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Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA

Inositol-1,4,5-trisphosphate (IP₃)-dependent Ca²⁺ release represents the major Ca²⁺ mobilizing pathway responsible for diverse functions in non-excitable cells. In the heart, however, its role is largely unknown or controversial. In intact cat atrial myocytes, endothelin (ET-1) increased basal [Ca²⁺]_i levels, enhanced action potential-evoked [Ca²⁺]_i transients, caused [Ca²⁺]_i transients with alternating amplitudes (Ca²⁺ alternans), and facilitated spontaneous Ca²⁺ release from the sarcoplasmic reticulum (SR) in the form of Ca²⁺ sparks and arrhythmogenic Ca²⁺ waves. These effects were prevented by the IP₃ receptor (IP₃R) blocker aminoethoxydiphenyl borate (2-APB), suggesting the involvement of IP₃-dependent SR Ca²⁺ release. In saponin-permeabilized myocytes IP₃ and the more potent IP₃R agonist adenophostin increased basal [Ca²⁺]_i and the frequency of spontaneous Ca²⁺ sparks. In the presence of tetracaine to eliminate Ca²⁺ release from ryanodine receptor (RyR) SR Ca²⁺ release channels, IP₃ and adenophostin triggered unique elementary, non-propagating IP₃R-dependent Ca²⁺ release events with amplitudes and kinetics that were distinctly different from classical RyR-dependent Ca²⁺ sparks. The effects of IP₃ and adenophostin were prevented by heparin and 2-APB. The data suggest that IP₃-dependent Ca²⁺ release increases [Ca²⁺]_i in the vicinity of RyRs and thus facilitates Ca²⁺-induced Ca²⁺ release during excitation–contraction coupling. It is concluded that in the adult mammalian atrium IP₃-dependent Ca²⁺ release enhances atrial Ca²⁺ signalling and exerts a positive inotropic effect. In addition, by facilitating Ca²⁺ release, IP₃ may also be an important component in the development of Ca²⁺-mediated atrial arrhythmias.

(Received 21 November 2003; accepted after revision 26 January 2004; first published online 30 January 2004)
Corresponding author L. A. Blatter: Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 S. First Ave., Maywood, IL 60153, USA. Email: lblatte{at}lumc.edu

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