Effect of pentobarbital on Na and Ca action potentials in an invertebrate neuron

It has been suggested that Ca currents may be more sensitive to barbiturate blockade than Na currents. This hypothesis has been tested by comparing the effect of pentobarbital (PB) on the maximum rate of rise (V̇_max) of Ca-dependent and Na-dependent action potentials in cell R₂ of the Aplysia abdominal ganglion. In Ca-free medium ([Na]₀ = 494 mM), V̇_max of Na-spikes ranged from 50 to 100 V/s, while in Na-free medium ([Ca]₀ = 30 mM), V̇_max of Ca-spikes ranged from 7 to 20 V/s. Under these conditions, Ca-spikes were 3-4 times more sensitive to barbiturate blockade than were Na-spikes. However, it was found that the sensitivity of Na- and Ca-spikes to PB depended on V̇_max of the spike prior to drug addition. V̇_max was manipulated by altering the driving force on the current carrying cation; this was accomplished by changing the concentration of the cation in the bathing medium. Thus, Ca-spikes, elicited in media containing 10 mM Ca, were more sensitive to PB than were Ca-spikes elicited in 30 mM Ca. Likewise, the sensitivity of Na-spikes to PB could be altered by changing the external Na concentration, and consequently, V̇_max. When the external Na and Ca concentrations were adjusted so that V̇_max of Na- and Ca-spikes were similar, prior to drug addition, the PB dose-response curves for Na- and Ca-spikes overlapped. The mechanism accounting for the dependence of PB sensitivity on V̇_max prior to drug addition remains unclear. However, the observation that PB dose-response curves for Na- and Ca-spikes are similar when V̇_max of the spikes is similar, suggests that Na and Ca currents may be equally sensitive to PB in this particular cell.