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

Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2303-9. doi: 10.1152/ajpheart.2000.279.5.H2303.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Diastole / physiology*
  • Ion Transport / drug effects
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Patch-Clamp Techniques
  • Rabbits
  • Sinoatrial Node / metabolism*
  • Sodium / metabolism*
  • Sodium Channel Blockers
  • Sodium Channels / metabolism*
  • Tetrodotoxin / pharmacology


  • Sodium Channel Blockers
  • Sodium Channels
  • Tetrodotoxin
  • Sodium