From syncitium to regulated pump: A cardiac muscle cellular update

The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information on Ca²⁺ 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 local Ca²⁺ cycling in sinoatrial nodal cells (SANCs) as a mechanism underlying cardiac automaticity is also presented as part of the recently described coupled-clock pacemaker system. The details of this regulation are emerging; however, the notion that the sequestration and release of Ca²⁺ from internal stores in SANCs (similar to that observed in ventricular myocytes) regulates the rhythmic excitation of the heart (i.e., membrane ion channels) is an important advancement in this area. The regulatory role of cardiac adrenergic receptors on cardiac rate and function is also included, and fundamental concepts related to intracellular signaling are discussed. An important point of emphasis is that whole organ cardiac dynamics can be traced back to cellular events regulating intracellular Ca²⁺ homeostasis and, as such, provides an important conceptual framework from which students can begin to think about whole organ physiology in health and disease. Greater synchrony of Ca²⁺-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle.