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Modulation of calcium channels in arterial smooth muscle cells by dihydropyridine enantiomers

Hering, S; Hughes, AD; Timin, EN; Bolton, TB; (1993) Modulation of calcium channels in arterial smooth muscle cells by dihydropyridine enantiomers. The Journal of General Physiology , 101 (3) 393 - 410. 10.1085/jgp.101.3.393. Green open access

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Abstract

The actions of the optical enantiomers of BAY K 8644 and Sandoz 202,791 were studied on barium inward currents recorded using the whole-cell configuration of the patch clamp technique from enzymatically isolated smooth muscle cells from the rabbit ear artery. The enantiomers were applied by bath perfusion or rapidly by a concentration jump technique, which enabled the study of drug action under equilibrium and nonequilibrium conditions. A larger effect of agonists was seen on peak inward current in 110 mM Ba when small rather than large depolarizations were applied. The midpoint voltage of the steady-state inactivation curve of IBa was -12.8 +/- 1.9 mV (n = 4) in the absence of drug, -16.4 +/- 2.5 mV (n = 4) in 1 microM (+)202,791, and -31.4 +/- 0.4 mV (n = 4) in 1 microM (-)202,791. The rate of onset of action of the agonist and antagonist enantiomers of BAY K 8644 and Sandoz 202,791 was studied by rapid application during 20-ms depolarizing steps from different holding potentials to +30 mV at 1 or 0.2 Hz. The drugs were applied as concentration jumps between two single pulses of a pulse train. The rates of onset of drug action on peak IBa during a 1-Hz pulse train were concentration dependent over the range of 100 nM-3 microM for both (+) and (-)202,791. The rate of onset of inhibition of peak current by antagonist enantiomers was not significantly influenced by the test pulse frequency. At a holding potential of -60 mV, the onset rate of the increase in peak IBa on application of 1 microM of agonist enantiomers (+)202,791 or (-)BAY K 8644 during a train of pulses occurred with mean time constants of 2.1 +/- 0.7 s (n = 7) and 2.3 +/- 0.2 s (n = 4), respectively. The onset of current increase on application of 1 microM (+)202,791 during a single voltage clamp step to 20 mV was faster, with a mean time constant of 380 +/- 80 ms (n = 3).

Type: Article
Title: Modulation of calcium channels in arterial smooth muscle cells by dihydropyridine enantiomers
Location: UNITED STATES
Open access status: An open access version is available from UCL Discovery
DOI: 10.1085/jgp.101.3.393
Publisher version: http://dx.doi.org/10.1085/jgp.101.3.393
Language: English
Additional information: © 1993 Rockefeller University Press Originally published in The Journal of General Physiology. doi:10.1085/jgp.101.3.393. PMCID: PMC2216766 Publication available under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode. This provides the non-exclusive right to copy, distribute, or display the Work is granted after six months of publication.
Keywords: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Animals, Arteries, Barium, Calcium Channel Agonists, Calcium Channel Blockers, Calcium Channels, Dihydropyridines, Membrane Potentials, Muscle, Smooth, Vascular, Rabbits, Stereoisomerism
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1416125
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