Modulation of voltage-activated channels by calcitonin gene-related peptide in cultured rat neurones

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