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APS REFRESHER COURSE REPORT

REGULATION OF CARDIAC EXCITATION-CONTRACTION COUPLING: A CELLULAR UPDATE

The Noll Physiological Research Center and Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania 16802

Abstract

The primary purpose of this paper is to present a basic overview of some "relatively" new ideas related to the regulation of cardiac performance and underlying excitation-contraction (EC) coupling that have yet to be incorporated to textbooks currently used for introductory graduate-level physiology courses. Within the context of cardiac EC coupling, this review incorporates information on microdomains and local control theory, with particular emphasis on the role of Ca²⁺ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to Ca²⁺ release mechanisms specific to the sarcoplasmic reticulum is also presented, as well as the idea of the ryanodine receptor as a macromolecular signaling complex. Because of the potential relationship to maladaptive functional responses under conditions of cardiovascular pathology, the regulatory role of cardiac adrenergic and additional G protein-coupled receptors known to regulate cardiac function is included, and fundamental concepts related to intracellular signaling are discussed. Finally, information on the roles of vascular and cardiac nitric oxide as an important regulator of cardiac performance is included to allow students to begin to think about the ubiquitous role of nitric oxide in the regulation of the cardiovascular system. An important point of emphasis is that whole organ cardiac dynamics can be traced back to the cellular events regulating intracellular Ca²⁺ homeostasis and as such provides an important conceptual framework from which the students can begin to think about whole organ physiology in health and disease.

Key words: review; myocardium; Ca²⁺ sparks; G protein-coupled receptors; ryanodine receptor; nitric oxide