A BIPHASIC DOPAMINERGIC MODULATION OF THE HIGH VOLTAGE-ACTIVATED BA2+CURRENT OF IDENTIFIED SNAIL NEURONS

We have investigated the intracellular mechanisms by which dopamine in duced a biphasic modulation of the Ba2+ current amplitude through the high voltage-activated Ca2+ channel (HVA-I-Ba) in identified Helix asp ersa neurons. We used the two electrode voltage clamp technique on a g roup of identified neurons of the right parietal ganglion in situ, and the whole cell patch clamp technique on these same neurons in primary culture. Brief application of dopamine induced an initial fast reduct ion of the HVA-I-Ba followed by a slower enhancement of HVA-I-Ba. This enhancement was not due to a shift of the current-voltage curve. Repe titive application of dopamine did not attenuate this phase of the res ponse. During longer application, the inhibition began to 'sag' and re turned towards control levels. These results indicate that the enhance ment was not due to a desensitization of the receptor or a relief from tonic G-protein mediated inhibition of the current. Manipulations of the levels of intracellular second messengers such as Ca2+, cGMP, cAMP , and arachidonic acid, as well as inhibition of protein kinases and p hosphatases, had no effect on the dopamine induced biphasic effect on HVA-I-Ba. Pertussis toxin added to the patch pipette had a slow but si multaneous blocking effect on both phases of the dopamine action on HV A-I-Ba. Since our results show that pertussis toxin affects both phase s of the dopamine action on this current, we suggest that both phases of the dopamine action on HVA-I-Ba are mediated by a pertussis toxin-s ensitive G-protein. Ii a second messenger is implicated, it is none of the 'classical' second messenger systems.