Cs+ loading reveals Na+-dependent persistent inward current and negative slope resistance region in Aplysia giant neurons.

Abstract
The giant, nonbursting neurons R2 and LP1 of A. californica were loaded iontophoretically with Cs+ to study the slow inward current and its ionic sensitivity, in isolation from K+ outward currents. In the relative absence of the normally large K+ outward currents, a persistent net inward current and concomitant negative slope resistance region of the current-voltage relationship was shown to be enhanced, if already present, or revealed, if not present prior to Cs+ loading. The slow inward current and negative slope resistance region of the Cs+-loaded neurons showed a marked, concentration-dependent sensitivity to external Na+ concentration. Increases in external Ca2+ reduced the negative slope resistance region and slow inward current. Both of these were insensitive to decreasing Ca2+ or even replacement of Ca2+ with Co2+. An increase in external Mg2+ had an effect similar to an increase in external Ca2+ on the slow inward current and negative slope resistance region. A major portion of the slow inward current and negative slope resistance regions of these nonbursting neurons is caused by a slowly inactivating membrane conductance to Na+. The persistence of this current makes it part of the slow membrane current system affecting spike frequency during prolonged depolarizations.