112 THE AGE DEPENDENCY OF MYOCARDIAL EXCITATION CONTRACTION COUPLING

Abstract

Mechanisms of excitation-contraction coupling in mammalian ventricle may be age dependent. Accordingly, sucrose gap voltage clamp techniques were developed to control membrane potential while simultaneously measuring membrane current and developed tension in right ventricular pappilary muscles to compare newborn (NB) (less than 10 days of age) and adult (A) New Zealand white rabbits. Steady state net membrane currents generated by voltage clamp steps of varying amplitude were similar in the two age groups. However, clamp step induced tension in NB heart developed continously to a steady state level maintained for the length of the clamp step. Tension was a monotomically increasing function of membrane potential at all clamp durations. In contrast, clamp step induced tension in A heart developed an early peak and relaxed to a lower steady state level. Early phasic tension increased with increasing clamp potential from -60 to 0 mV and then declined with increasing clamp amplitude, while steady state tension increased monotonically with membrane potential. Since the characteristics of steady state tension and current are similar in the two age groups, we suggest the latter tension is generated by transport of calcium across the sarcolema by a mechanism present at birth, whereas the process of phasic tension matures with age, probably reflecting advancing formation and function of the sarcoplastic reticulum. It is clear that a developmental approach to cellular cardiac physiology is required to create a valid framework from which to view cardiac function and its therapeutic manipulation in the clinical setting.