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Am J Physiol Heart Circ Physiol 279: H2303-H2309, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 5, H2303-H2309, November 2000

Na+ current contribution to the diastolic depolarization in newborn rabbit SA node cells

Mirko Baruscotti1,2, Dario DiFrancesco2, and Richard B. Robinson1

1 Department of Pharmacology, Columbia University, New York, New York 10032; and 2 Dipartimento di Fisiologia e Biochimica Generali, Elettrofisiologia, Università di Milano, 20133 Milano, Italy

Isolated newborn, but not adult, rabbit sinoatrial node (SAN) cells exhibit spontaneous activity that (unlike adult) are highly sensitive to the Na+ current (INa) 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 INa during long step depolarizations. INa 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 INa at diastolic potentials, a small TTX-sensitive current flows during the diastolic depolarization in neonatal pacemaker myocytes.

sinoatrial node; slow inactivation; patch clamp


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