Calcitonin gene-related peptide enhances the rate of desensitization of the nicotinic acetylcholine receptor in cultured mouse muscle cells.

Abstract:

:Calcitonin gene-related peptide (CGRP) is a neuropeptide that coexists with acetylcholine in spinal cord motoneurons. The effects of CGRP on the functional properties of the nicotinic acetylcholine receptor (AcChoR) were examined by electrophysiological methods. Using the whole-cell patch-clamp technique and a mouse cell line derived from soleus muscle, we found that CGRP produces a progressive and reversible enhancement of the rapid-decay phase of AcChoR desensitization. Single-channel data further show that CGRP decreases acetylcholine-activated channel opening frequency. This decrease occurs when CGRP and acetylcholine are applied on different cell-surface areas and thus is likely mediated by a second-messenger system. CGRP is also shown to increase cAMP accumulation in this cell line. The effects of CGRP on macroscopic acetylcholine-activated currents are mimicked by external application of forskolin (10 microM) or by internal perfusion of the cell with cAMP (1 microM). In both these cases, further application of CGRP produces no additional enhancement of AcChoR desensitization. These results suggest that, on mouse muscle cells, CGRP regulates AcChoR desensitization by a mechanism that involves, at least in part, cAMP-dependent phosphorylation of the AcChoR.

authors

Mulle C,Benoit P,Pinset C,Roa M,Changeux JP

doi

10.1073/pnas.85.15.5728

subject

Has Abstract

pub_date

1988-08-01 00:00:00

pages

5728-32

issue

15

eissn

0027-8424

issn

1091-6490

journal_volume

85

pub_type

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