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Influence of postnatal changes in action potential duration on Na-Ca exchange in rabbit ventricular myocytes
Authors:Peter S. Haddock  Michael Artman  William A. Coetzee
Affiliation:(1) Department of Pediatrics, NYU Medical Center, New York, NY 10016, USA, US;(2) Department of Physiology and Neuroscience, NYU Medical Center, New York, NY 10016, USA, US;(3) Molecular and Cellular Research Laboratories, NYU Medical Center, Tisch Hospital (TH-501), 560 First Avenue, New York, NY 10016, USA, US
Abstract: Cardiac Na-Ca exchanger (NCX) expression and current density are significantly greater in newborn rabbit hearts compared with adults. However, the relatively short action potential (AP) at birth may limit the impact of increased NCX expression by diminishing Ca2+ entry via Na-Ca exchange current (I NaCa). To address the interdependence of AP duration and NCX activity, we voltage-clamped newborn (NB, 1–5 day), juvenile (JV, 10–14 day) and adult (AD) rabbit myocytes with a series of APs of progressively increasing duration (APD90: 108–378 ms) under nominally chloride-free conditions. In each age group we quantified an increase 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] despite the significantly shorter APD90 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 NB and JV but not AD myocytes (NB 4.8 ± 0.5, JV 1.2 ± 0.3% resting length). These data demonstrate that a shorter AP does not negate the impact of increased NCX expression at birth. Received: 23 September 1997 / Received after revision: 2 January 1998 / Accepted: 5 January 1998
Keywords:  Na-Ca exchange  Ca2+  Action potential  Voltage-clamp  Newborn  Development  Contraction
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