MODULATION OF VOLTAGE-ACTIVATED CHANNELS BY CALCITONIN GENE-RELATED PEPTIDE IN CULTURED RAT NEURONS

1. Whole-cell currents were recorded from cultures of dissociated neocortical neurones of the rat. Rat alpha-calcitonin gene-related peptide (CGRP; 1 nM-1-mu-M) caused significant dose-dependent decreases in the voltage-activated transient (A-current) and delayed rectifier K+ currents. Forskolin (10 nM-20-mu-M) mimicked this effect. Peak K+ currents were gradually decreased after loading neurones with cyclic AMP (100-mu-M) through patch pipettes. CGRP was ineffective in neurones loaded with cyclic AMP. 2. CGRP (0.5-2 mu-M) increased cytosolic cyclic AMP concentration and this effect was mimicked by forskolin (5-40 mu-M). 3. CGRP (0.1-1 mu-M) reduced high-threshold Ca2+ currents; as did forskolin (5-20 mu-M) and cyclic AMP loaded into the neurones. In contrast, low-threshold Ca2+ currents were not affected by any of these agents. 4. Voltage-activated Na+ currents were significantly reduced by both CGRP (0.1-1 mu-M) and forskolin (5-20 mu-M). A similar effect was observed when cells were loaded with cyclic AMP. 5. We conclude that, in neocortical neurones, CGRP attenuates voltage-activated currents by stimulating the intracellular cyclic AMP signalling system.