Differential effects of pentylenetetrazole on ion currents of Aplysia neurones

Abstract

The effects of the convulsant drug pentylenetetrazole (PTZ) on separated membrane current components has been studied in identified voltage-clamped Aplysia neurones. External PTZ blocks the voltage-dependent Na +,Ca 2+ currents and the delayed rectifier current (I Na, I Ca and I K,V, respectively). The amplitude of the Ca 2+-activated K + current (I K,Ca) is increased. The amplitude of the fast inactivating K + current (I A) is transiently increased at low concentrations of PTZ but is depressed at higher concentrations or after long-lasting application of the drug. The effect of PTZ on leakage current (I L) seems to depend on the cell type. In some cells (R-15, L-7, LP-1) I L is decreased while it is increased in other cells (L-11, BL-1, BR-1). PTZ accelerates the inactivation of I K,V and I A and shifts the current—voltage relation of I Ca to negative voltages by 5–8 mV. Pressure injection of PTZ into the neurone did not affect I K,V or I K,Ca. Thus PTZ seems to act on the outside of the plasma membrane. The effect of external PTZ on I Na, I Ca, I K,V and I L is also observed if the internal Ca 2+ activity is buffered with EGTA suggesting that an increase in the internal Ca 2+ activity is not involved. At −40 mV PTZ induces a tetrodotoxin-insensitive inward current carried by Na + ions. PTZ transforms the beating pacemaker cell L-11 into a bursting pacemaker and the bursting pacemaker cell R-15 exhibits ‘square-wave’-like oscillations of the membrane potential.