EFFECTS OF CLAMP RISE-TIME ON RAT-BRAIN IIA SODIUM-CHANNELS IN XENOPUS OOCYTES

The kinetic properties of wild-type rat brain IIa sodium channels in e xcised macropatches were studied using step depolarizations and ramp d epolarizations to imitate the slow settling-time of voltage in two-ele ctrode voltage clamp. Ramp depolarizations longer than 1 ms produce an increasing suppression of peak sodium current (I-Na). Two rates of in activation can be seen in macroscopic sodium current records from exci sed patches following both step and ramp depolarizations. During slow ramp depolarizations, reduction in peak I-Na is associated with select ive loss of the fastest rate of test-pulse inactivation. This change c an be interpreted as resulting from inactivation of a separate sub-pop ulation of 'fast mode' channels. The slow rate of test-pulse inactivat ion is relatively unaffected by changing ramp durations. These results are sufficient to explain the typically slow inactivation kinetics se en in two-electrode voltage clamp recordings of sodium channels in Xen opus oocytes. Thus, the kinetics of sodium channels expressed in Xenop us oocytes are not readily characterizable by two-electrode clamp beca use of the large membrane capacitance and resulting slow clamp settlin g time which artifactually selects for slow mode channels. (C) 1997 El sevier Science B.V.