Integration of myofilament response to Ca2+ with cardiac pump regulation and pump dynamics

Abstract

In this paper I present some ideas related to teaching cardiac pump dynamics and regulation to first-year medical students. I emphasize explicit presentation of the relation between the activity of the contractile machine in the myocytes to pump dynamics, pressure-volume relations, and cardiac output regulation, with matching oxygen supply to tissue demands serving as a focal point. Important ideas here are 1) the concept that regulation is at the cellular level of regulation; 2) that force and shortening properties of the cells are ultimately dependent on the number of cross bridges reacting with the thin filament and on the rate of cross-bridge cycling; 3) that the concepts of preload, aferload, and contractility originated in studies of muscle mechanics; 4) that there is a reserve of force-generating cross bridges, i.e., the myofilaments are not fully activated by Ca2+ in the basal state, and that force-generating cross bridges can themselves activate the thin filament; and 5) that length dependence of myofilament Ca2+ activation is important in the cellular basis of Starling's law of the heart. The elaboration of these processes serves to elucidate how these mechanisms play a role in coupling tissue oxygen demands to supply.