Abstract
Emerging evidence supports the idea that taurine exerts some of its actions through inhibition of inward rectifier K+ channels, ATP-sensitive K+ channels, and voltage-dependent K+ channels. However, to date not much is known about the effects of this sulfonic amino acid on Ca2+-activated K+ (KCa2+) channels, which are widely expressed in various tissues, including skeletal muscle. In the present work, the effects of taurine on KCa2+ channels of rat skeletal muscle fibers were investigated using the patch-clamp technique. The application of the amino acid to the internal side of the excised macropatches induced a dose-dependent decrease in the outward KCa2+ currents recorded at positive membrane potentials in the presence of 8 to 16 μM concentrations of free Ca2+ ions in the bath with an IC50 of 31.9 · 10−3 ± 1 M (slope factor = 1.2) (n = 11 patches). In contrast, at negative membrane potentials taurine caused an enhancement of the muscular inward KCa2+ currents with a DE50(drug concentration needed to enhance the current by 50%) of 46.7 · 10−3 ± 2 M (slope factor = 1.3) (n = 9 patches). Single channel analysis revealed that this effect was mediated by changes in the reversal potential of the KCa2+ channel for K+ ions with no changes in the gating properties or in the sensitivity of the channel to Ca2+ ions. Taurine also did not affect the single channel conductance. In conclusion, taurine shows a voltage-dependent dualistic action on KCa2+ channels, being an inhibitor of the channel at positive membrane potentials and an activator at negative membrane potentials.
Footnotes
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The financial support of Cofin-Ministero dell' Università e della Ricerca Scientifica e Tecnologica (MURST)1998–2000 is gratefully acknowledged.
- Abbreviations:
- KATP
- ATP-sensitive K+channel
- SUR
- sulfonylurea receptor
- KCa2+
- Ca2+-activated K+ channel
- MOPS
- 3-(N-morpholino)propanesulfonic acid
- Vm
- membrane potential
- DE50
- drug concentration needed to enhance the current by 50%
- FDB
- flexor digitorum brevis
- Received February 12, 2001.
- Accepted May 15, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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