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Na(+) current contribution to the diastolic depolarization in newborn rabbit SA node cells
M Baruscotti1, D DiFrancesco, R B Robinson
1Department of Pharmacology, Columbia University, New York, New York 10032, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|October 25, 2000
Summary
Neonatal rabbit sinoatrial node cells show TTX-sensitive sodium current (I(Na)) during diastolic depolarization, unlike adult cells. This difference is due to slow inactivation of I(Na) at diastolic potentials in newborn pacemaker myocytes.
Area of Science:
- Electrophysiology
- Cardiovascular Physiology
- Neonatal Cardiology
Background:
- Sinoatrial node (SAN) cells in newborns exhibit spontaneous activity sensitive to tetrodotoxin (TTX), unlike adult cells.
- This sensitivity suggests a distinct role for sodium current (I(Na)) in neonatal cardiac pacemaking.
Purpose of the Study:
- To investigate the electrophysiological basis for TTX sensitivity in newborn rabbit SAN cells.
- To characterize the properties of TTX-sensitive currents during the pacemaker phase.
Main Methods:
- Voltage clamp recordings from isolated rabbit SAN cells (newborn and adult).
- Ramp depolarizations mimicking pacemaker potential, preceded by step depolarizations.
- Analysis of TTX-sensitive currents and their inactivation kinetics.
Main Results:
- A TTX-sensitive current was observed in newborn, but not adult, SAN cells during ramp depolarizations.
- This current, while reduced by preceding action potentials, was not abolished, indicating a kinetic basis.
- Slow inactivation of I(Na) at diastolic potentials was identified as the mechanism responsible for the persistent TTX-sensitive current.
Conclusions:
- A small, TTX-sensitive sodium current flows during diastolic depolarization in neonatal pacemaker myocytes.
- Slow inactivation of I(Na) at diastolic potentials explains the unique TTX sensitivity of newborn SAN cells.
- This finding highlights developmental differences in cardiac pacemaking mechanisms.