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Structural and biophysical determinants of single CaV3.1 and CaV3.2 T-type calcium channel inhibition by N2O.
- Source :
- Cell Calcium; Oct2009, Vol. 46 Issue 4, p293-302, 10p
- Publication Year :
- 2009
-
Abstract
- Abstract: We investigated the biophysical mechanism of inhibition of recombinant T-type calcium channels Ca<subscript>V</subscript>3.1 and Ca<subscript>V</subscript>3.2 by nitrous oxide (N<subscript>2</subscript>O). To identify functionally important channel structures, chimeras with reciprocal exchange of the N-terminal domains I and II and C-terminal domains III and IV were examined. In whole-cell recordings N<subscript>2</subscript>O significantly inhibited Ca<subscript>V</subscript>3.2, and – less pronounced – Ca<subscript>V</subscript>3.1. A Ca<subscript>V</subscript>3.2-prevalent inhibition of peak currents was also detected in cell-attached multi-channel patches. In cell-attached patches containing ≤3 channels N<subscript>2</subscript>O reduced average peak current of Ca<subscript>V</subscript>3.2 by decreasing open probability and open time duration. Effects on Ca<subscript>V</subscript>3.1 were smaller and mediated by a reduced fraction of sweeps containing channel activity. Without drug, single Ca<subscript>V</subscript>3.1 channels were significantly less active than Ca<subscript>V</subscript>3.2. Chimeras revealed that domains III and IV control basal gating properties. Domains I and II, in particular a histidine residue within Ca<subscript>V</subscript>3.2 (H191), are responsible for the subtype-prevalent N<subscript>2</subscript>O inhibition. Our study demonstrates the biophysical (open times, open probability) and structural (domains I and II) basis of action of N<subscript>2</subscript>O on Ca<subscript>V</subscript>3.2. Such a fingerprint of single channels can help identifying the molecular nature of native channels. This is exemplified by a characterization of single channels expressed in human hMTC cells as functional homologues of recombinant Ca<subscript>V</subscript>3.1. [Copyright &y& Elsevier]
- Subjects :
- CALCIUM channels
NITROUS oxide
MOSAICISM
BIOPHYSICS
CELL physiology
Subjects
Details
- Language :
- English
- ISSN :
- 01434160
- Volume :
- 46
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Cell Calcium
- Publication Type :
- Academic Journal
- Accession number :
- 44701188
- Full Text :
- https://doi.org/10.1016/j.ceca.2009.09.002