Ca2+ channel kinetics in acutely isolated fetal, neonatal, and adult rabbit cardiac myocytes.
Measurement of transsarcolemmal voltage-gated Ca2+ current (ICa) in myocytes isolated from immature rabbit heart has demonstrated an unexpectedly low level of Ca2+ channel activity. We have characterized the kinetic properties of ICa in acutely isolated 21-day fetal, 1-5-day-old neonatal, and adult cardiac myocytes by the whole-cell voltage-clamp technique. The membrane potential for half-maximal steady-state inactivation became less negative with maturation (-24 +/- 3 [mean +/- SEM] mV, n = 5; -19 +/- 2 mV, n = 5; and -11 +/- 2 mV, n = 6 for fetal, neonatal, and adult myocytes, respectively; p < 0.005). In contrast, the membrane potential for half-maximal steady-state activation was not statistically different among the age groups studied. These parameters accurately predicted the voltage dependence of the sustained ICa present at the end of a 400-msec depolarization. This "window" current was significantly smaller in immature cells than in adult cells and occurred at a more negative membrane potential in the younger age groups. The time course of inactivation of ICa was not significantly different between age groups. However, ICa was inhibited by increasing the frequency of stimulation. This effect was most prominent in immature cells, particularly at more positive holding potentials. This developmental alteration in the frequency dependence of ICa was due in part to a prolonged time constant of recovery from inactivation in the younger age groups. In summary, the kinetic properties of ICa in immature cardiac cells place them at a relative disadvantage in terms of the total Ca2+ influx during a depolarization. Thus, the role of ICa in the control of cell contraction may change with development.
Department of Pediatrics, University of California, Los Angeles 90024.
G T
GT
Wetzel
F
F
Chen
T S
TS
Klitzner
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D004594:Electrophysiology; D005333:Fetus / Q000378:metabolism*; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006352:Heart Ventricles; D006706:Homeostasis; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D013997:Time Factors
D015220:Calcium Channels