Photoinduced Removal of Nifedipine Reveals Mechanisms of Calcium Antagonist Action on Single Heart Cells
Abstract
The currents through voltage-activated calcium channels in heart cell membranes are suppressed by dihydropyridine calcium antagonists such as nifedipine. Nifedipine is photolabile, and the reduction of current amplitude by this drug can be reversed within a few milliseconds after a 1-ms light flash. The blockade by nifedipine and its removal by flashes were studied in isolated myocytes from neonatal rat heart using the whole-cell clamp method. The results suggest that nifedipine interacts with closed, open, and inactivated calcium channels. It is likely that at the normal resting potential of cardiac cells, the suppression of current amplitude arises because nifedipine binds to and stabilizes channels in the resting, closed state. Inhibition is enhanced at depolarized membrane potentials, where interaction with inactivated channels may also become important. Additional block of open channels is suggested when currents are carried by Ba^(2+) but is not indicated with Ca^(2+) currents. Numerical simulations reproduce the experimental observations with molecular dissociation constants on the order of 10^(-7) M for closed and open channels and 10^(-8) M for inactivated channels.
Additional Information
© 1985 The Rockefeller University Press. After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode, or updates thereof. Original version received 4 December 1984 and accepted version received 7 May 1985. This work was supported by the Del E. Webb Foundation (fellowship to A.M.G.), Fulbright Hayes (travel grant to A.M.G.), the Los Angeles Affiliate of the American Heart Association (fellowships to A.M.G. and J.M.N.), the National Office of the American Heart Association (established investigatorship to J.M.N.), and the National Institutes of Health (grant GM-29836).Attached Files
Published - GURjgp85.pdf
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Additional details
- PMCID
- PMC2228798
- Eprint ID
- 32181
- Resolver ID
- CaltechAUTHORS:20120629-070830645
- Del E. Webb Foundation
- Fullbright Hayes
- American Heart Association, Los Angeles Affiliate
- American Heart Association, National Office
- NIH
- GM-29836
- Created
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2012-07-02Created from EPrint's datestamp field
- Updated
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2021-11-09Created from EPrint's last_modified field