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

Abstract

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 microM) caused significant dose‐dependent decreases in the voltage‐activated transient (A‐current) and delayed rectifier K+ currents. Forskolin (10 nM‐20 microM) mimicked this effect. Peak K+ currents were gradually decreased after loading neurones with cyclic AMP (100 microM) through patch pipettes. CGRP was ineffective in neurones loaded with cyclic AMP. 2. CGRP (0.5‐2 microM) increased cytosolic cyclic AMP concentration and this effect was mimicked by forskolin (5‐40 microM). 3. CGRP (0.1‐1 microM) reduced high‐threshold Ca2+ currents; as did forskolin (5‐20 microM) 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 microM) and forskolin (5‐20 microM). 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. © 1991 The Physiological Society