DO NEURONS FROM RAT NEOSTRIATUM EXPRESS BOTH A TTX-SENSITIVE AND A TTX-INSENSITIVE SLOW NA+ CURRENT

1. The properties of a tetrodotoxin (TTX)-sensitive, persistent Na+ current and a purported TTX-insensitive slow Na+ current were studied in acutely isolated neurons from rat neostriatum with the use of the whole cell configuration of the patch-clamp technique. 2. A TTX-sensitive, persistent Na+ current (I-NaP) was activated positive to -60 mV and reached a peak amplitude of -40 to -120 pA at about -40 mV. As indicated by slow depolarizing voltage ramps, activation of I-NaP did not require preceding activation of the fast, rapidly inactivating Na+ current. 3. The current-voltage (I-V) relationship of I-NaP displayed an unexpected inflection after passing through its peak value near -40 mV. Between -40 and -10 mV, I-NaP declined more rapidly with depolarization than it did at more depolarized potentials. The corresponding conductance (G(NaP)) peaked at -40 mV and declined to a smaller limiting value at potentials positive to about -10 mV. 4. This behavior is not consistent with the notion that I-NaP arises solely from a bell-shaped window conductance that results from the overlapping steady-state activation and inactivation curves of the fast Na+ current in a narrow voltage range, nor with the notion that I-NaP is generated by a single uniform conductance independent of the fast Na+ current. 5. In addition to I-NaP a second slow inward current (I-s) was evoked when small monovalent cations were omitted from the internal solution. I-NaP and I-s were present both in cells resembling medium spiny neurons and in cells resembling aspiny interneurons. 6. I-s was insensitive to TTX (1.2 mu M) and the Ca2+ channel blocker, cadmium. I-s was activated positive to about -45 mV and attained a maximum amplitude of -200 to -500 pA close to 0 mV. The kinetic and pharmacological profile of this current was almost identical to that of a slow Na+ current (I-NaS) recently described in the same preparation. 7. To our surprise, I-s, but not I-NaP, disappeared when whole cell recordings were performed in solutions with physiological cation concentrations, or when high Cs+ was present in the internal solution. 8. Our data provide evidence for a persistent, TTX-sensitive Na+ current, the features of which suggest that it should influence the intrinsic excitability of neostriatal neurons in the subthreshold voltage region. We failed, however, to identify a TTX-insensitive slow Na+ current when physiological cation gradients were established.