Modulation of voltage-activated channels by calcitonin gene-related peptide in cultured rat neurones.
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.
Zona
C
C
Dipartimento di Medicina Sperimentale, Universitá dell'Aquila, Italy.
Farini
D
D
Palma
E
E
Eusebi
F
F
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D007473:Ion Channels; D005576:Colforsin; D012964:Sodium; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D002118:Calcium