Isolated newborn, but not adult, rabbit sinoatrial node (SAN) cells exhibit spontaneous activity that (unlike adult) are highly sensitive to the Na+ current (I-Na) blocker TTX. To investigate this TTX action on automaticity, cells were voltage clamped with ramp depolarizations mimicking the pacemaker phase of spontaneous cells (-60 to -20 mV, 35 mV/s). Ramps elicited a TTX-sensitive current in newborn (peak density 0.89 +/- 0.14 pA/pF, n = 24) but not adult (n = 5) cells. When depolarizing ramps were preceded by steplike depolarizations to mimic action potentials, ramp current decreased 54.6 +/- 8.0% (n = 3) but was not abolished. Additional experiments demonstrated that ramp current amplitude depended on the slope of the ramp and that TTX did not alter steady-state holding current at pacemaker potentials. This excluded a steady-state Na+ window component and suggested a kinetic basis, which was investigated by measuring TTX-sensitive I-Na during long step depolarizations. I-Na exhibited a slow but complete inactivation time course at pacemaker voltages (tau = 33.9 +/- 3.9 ms at -50 mV), consistent with the rate-dependent ramp data. The data indicate that owing to slow inactivation of I-Na at diastolic potentials, a small TTX-sensitive current flows during the diastolic depolarization in neonatal pacemaker myocytes.
|Titolo:||Na+ current contribution to the diastolic depolarization in newborn rabbit SA node cells|
|Autori interni:||BARUSCOTTI, MIRKO (Primo)|
DI FRANCESCO, DARIO (Secondo)
|Parole Chiave:||Patch clamp; Sinoatrial node; Slow inactivation|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||2000|
|Appare nelle tipologie:||01 - Articolo su periodico|