| Autor: |
duBell WH; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore 21201, USA., Wright PA, Lederer WJ, Rogers TB |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of physiology [J Physiol] 1997 Jun 15; Vol. 501 ( Pt 3), pp. 509-16. |
| DOI: |
10.1111/j.1469-7793.1997.509bm.x |
| Abstrakt: |
1. We examined the effects of the immunosupressant drug FK506 on excitation-contraction coupling in isolated rat ventricular myocytes. [Ca2+]i transients were recorded using the intracellular Ca2+ indicators fluo-3 and indo-1 while action potentials (APs) or membrane currents were recorded using patch-type microelectrodes in the whole cell mode. 2. FK506 (25 microM) rapidly and reversibly increased the magnitude of the [Ca2+]i transient in intact cells without changing resting [Ca2+]i or the kinetics of the [Ca2+]i transient, a finding consistent with previous reports that investigated the actions of FK506 on the sarcoplasmic reticulum Ca2+ release channel. 3. The 36% increase in the [Ca2+]i transient produced by FK506 was accompanied by a 293% increase in AP duration (by 293%). Importantly, the addition of FK506 had no effect on the [Ca2+]i transient when the depolarizing duration was controlled in voltage clamp experiments. The increased AP duration could be explained by a marked inward shift in the net membrane current that was observed in these experiments. 4. The net inward current change was not directly responsible for a change in Ca2+ influx, since no change in L-type Ca2+ current (ICa) was observed. Instead, FK506 inhibited both the transient outward K+ current (Ito) and the delayed rectifier K+ current (IK). 5. We conclude that FK506 increases the [Ca2+]i transient during normal contractions by an indirect action: it prolongs the action potential. This action does not appear to depend on the established action of FK506 on the ryanodine receptor. Instead, the inhibition of outward K+ currents prolongs the AP which secondarily increases Ca2+ influx and/or decreases Ca2+ efflux. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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