THE MODULATION OF CALCIUM-CHANNEL CURRENTS RECORDED FROM ADULT-RAT DORSAL RAPHE NEURONS BY 5-HT1A RECEPTOR OR DIRECT G-PROTEIN ACTIVATION

The effect 5-HT1A receptor activation on the temperature dependence of HVA calcium Channel currents has been studied in acutely isolated DR neurones, using barium as the charge carrier. 8-OH-DPAT caused a reduc tion in the temperature dependence of the peak current amplitude. Howe ver the most dramatic effect of 8-OH-DPAT was a large reduction in Q(1 0) for the current activation rate. This also occured with direct G-pr otein activation using GTP gamma S. In the presence of GTP gamma S, cu rrent activation became bi-exponential, rather than mono-exponential a s in the control situation. The time constants of both components were significantly slower than the controls, and the Q(10) for both compon ents was significantly lower. GDP beta S had no effect on the temperat ure dependence or kinetics of activation of HVA current. Depolarizing prepulses applied prior to test pulses were able to reverse the action of 8-OH-DPAT on the Q(10) of the activation rate. When prepulses were applied to cells containing GTP gamma S, the activation rate Q(10) wa s similar to control values. We postulate that the highly significant reduction in activation rate Q(10), seen with both 8-OH-DPAT and GTP g amma S, is as a result of a change in the mechanism underlying activat ion of HVA channels on depolarization. Contrary to previous models of calcium current modulation our results show that the mechanisms respon sible for slowed activation by transmitters and facilitation of the re sidual current by depolarizing prepulses have little in common. We pre sent a new model of transmitter modulation of HVA current, consistent with a mechanistic approach to channel subunit structure.