UMMS Affiliation

Department of Pharmacology; Worcester Foundation for Experimental Biology

Date

9-1-1994

Document Type

Article

Subjects

3-Pyridinecarboxylic acid,; 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl; ester; Animals; Calcium Channels; Dihydropyridines; Electrophysiology; Ethanol; Ion Channel Gating; Nerve Endings; Pituitary Gland, Posterior; Rats; Rats, Inbred Strains

Disciplines

Biochemistry

Abstract

Ingestion of ethanol results in a decreased level of plasma vasopressin, which appears to be caused by inhibition of arginine vasopressin (AVP) release from the neurohypophysis. Activation of membrane voltage-gated Ca2+ channels plays an important role in triggering this neurohormone release. In this article, single-channel recordings are used to demonstrate that ethanol, at concentrations constituting legal intoxication, inhibits dihydropyridine-sensitive "L-type" Ca2+ channels in isolated nerve terminals of the rat neurohypophysis. Ethanol reduced the channel open probability in a concentration-dependent manner. To allow finer resolution of channel openings and to better characterize the mechanisms of ethanol action, Bay K 8644 was used to prolong the openings of L-type Ca2+ channels. In the presence of this dihydropyridine (DHP), the reduction of the channel open probability by concentrations of ethanol of 25 mM or higher could be determined to be due primarily, although not completely, to a shortening of the open duration of this L-channel. Channel conductance was unaffected by ethanol, even at high concentrations. These results are consistent with previous macroscopic data indicating that calcium channels in these peptidergic terminals are targets for ethanol action, and indicate that ethanol acts directly on the gating characteristics of the L-type channel. Furthermore, examination of open and closed state transitions, as well as Hill plot analysis, suggests that ethanol's effects on gating are consistent with the interaction of a single drug molecule with a single target site, possibly the L-channel itself.

Rights and Permissions

Citation: J Neurosci. 1994 Sep;14(9):5453-60.

Related Resources

Link to Article in PubMed

Journal Title

The Journal of neuroscience : the official journal of the Society for Neuroscience 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester)

PubMed ID

7521910

Included in

Biochemistry Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.