INFLUENCE OF POSTNATAL CHANGES IN ACTION-POTENTIAL DURATION ON NA-CA EXCHANGE IN RABBIT VENTRICULAR MYOCYTES

Cardiac Na-Ca exchanger (NCX) expression and current density are signi ficantly greater in newborn rabbit hearts compared with adults. Howeve r, the relatively short action potential (AP) at birth may limit the i mpact of increased NCX expression by diminishing Ca2+ entry via Na-Ca exchange current (I-NaCa). TO address the interdependence of AP durati on and NCX activity, we voltage-clamped newborn (NB, 1-5 day), juvenil e (JV, 10-14 day) and adult (AD) rabbit myocytes with a series of APs of progressively increasing duration (APD(90): 108-378 ms) under nomin ally chloride-free conditions. In each age group we quantified an incr ease in outward (Q(Exout)) and inward (Q(Exin)) Ni2+-sensitive charge movement in response to AP prolongation. Q(Exout) and Q(Exin) measured during age-appropriate APs declined postnatally [Q(Exout): NB (2 day) 0.19 +/- 0.02, JV (10 day) 0.10 +/- 0.01, AD 0.04 +/- 0.002; Q(EXin): NB -0.2 +/- 0.01, JV -0.11 +/- 0.02; AD -0.04 +/- 0.003 pC/pF] despit e the significantly shorter APD(90) of newborn myocytes (NB 122 +/- 10 ; AD 268 +/- 22 ms). When Ca2+ fluxes by other transport pathways were blocked with nifedipine, ryanodine and thapsigargin, age-appropriate APs elicited contractions in NE and JV but not AD myocytes (NB 4.8 +/- 0.5, JV 1.2 +/- 0.3% resting length). These data demonstrate that a s horter AP does not negate the impact of increased NCX expression at bi rth.