Evidence for Developmental Changes in Sodium Channel Inactivation Gating and Sodium Channel Block by Phenytoin in Rat Cardiac Myocytes

The voltage-dependent properties of the voltage-activated sodium channel were studied in neonatal (1–2-day-old) and adult rat ventricular cardiac myocytes using the whole-cell variation of the patch-clamp technique (16°C, [Na]i=15 mM, [Na]o=25 mM). The voltage dependence of the sodium conductance-membrane potential relation was similar in both neonatal and adult myocytes except for a difference in slope; the adult sodium conductance-membrane potential relation was slightly more steep. Neonatal cells also differed from adult cells by demonstrating a more negative voltage midpoint of their sodium availability curve, a slower rate of recovery from inactivation at hyperpolarized potentials, and a greater extent of slow inactivation development compared with adult cells. Phenytoin (40 μM) reduced the sodium current in a tonic and use-dependent manner in both adult and neonatal myocytes. However, phenytoin (40 μM) produced significantly more tonic block at negative holding potentials (e.g., −140 mV) in neonatal myocytes (22±5% [mean±SEMI, n=14) than in adult myocytes (10±2%, n=11) (p