|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 101, 393-410, Copyright © 1993 by The Rockefeller University Press
ARTICLES |
S Hering, AD Hughes, EN Timin and TB Bolton
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, United Kingdom.
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).
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  U. C. Luft, R. Bychkov, M. Gollasch, V. Gross, J.-B. Roullet, D. A. McCarron, C. Ried, F. Hofmann, Y. Yagil, C. Yagil, et al. Farnesol Blocks the L-Type Ca2+ Channel by Targeting the {alpha}1C Subunit Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 959 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mitterdorfer, Z. Wang, M. J. Sinnegger, S. Hering, J. Striessnig, M. Grabner, and H. Glossmann Two Amino Acid Residues in the IIIS5 Segment of L-Type Calcium Channels Differentially Contribute to 1,4-Dihydropyridine Sensitivity J. Biol. Chem., November 29, 1996; 271(48): 30330 - 30335. [Abstract] [Full Text] [PDF]
|
|
|
|
