Whole-cell voltage clamp techniques were used to characterize the kinetics of I(Na) in immature (P3-5) and older (P > 25) acutely isolated rat CA1 hippocampal neurones. Fast-rising and fast-inactivating currents were recorded at all stages of maturation, evocable from V(m) values of -55 to -50 mV. Currents were sensitive to TTX (1 μM) and to sodium removal from the perfusate. Current density and maximum slope conductance increased with maturation. Current decay was described by two exponentials, the faster component dominating at 35 mV or more depolarized V(m) values; the ratio fast/slow inactivating component decreased with maturation. The voltage-dependence of conductance was taken as an approximation of m(∞). In younger cells, V( 1/2 ) values of the steady-state inactivation (h(∞)) and activation curves (m(∞)) were depolarized. Shifts of h(∞) and m(∞) curves were accompanied by shifts in the corresponding τ(h) and τ(m) voltage-dependence curves. In younger cells, activation curves had comparatively higher slope factors (V(s)), which is an indication of a lower voltage sensitivity of activation. m(∞), τ(m), h(∞), and τ(h) parameters were used to calculate the forward and backward activation and inactivation rate constants (α(m), β(m), α(h) and β(h)). P3-5 cells had relatively higher β(m) values accounting for the lower voltage sensitivity of activation. The findings are an indication of a dominant channel variety in the younger cells with a closed state higher probability. The results are consistent with lower depolarization rates previously reported in CA1 cells at early stages of maturation. Faster inactivation due to poor expression of the slower inactivating component may compensate for poorer repolarization mechanisms due to the immaturity of outward currents previously reported at early stages of maturation.
- Rate constant
- Sodium current