Phenotype-dependent functional and pharmacological properties of BK channels in skeletal muscle: effects of microgravity.
We investigated the involvement of calcium-activated potassium channel (BK) in skeletal muscle phenotype determination and response to acetazolamide, a BK opener. The BKs of slow-twitching soleus (SOL) and fast-twitching flexor digitorum brevis (FDB) muscles of the rat were investigated by patch-clamp technique. The changes of BK properties following muscle disuse were investigated in the hindlimb-unloaded (HU) rat, an animal model of disuse/microgravity. Two functionally different BKs were found in skeletal muscle. The BK of FDB was sensitive to calcium and to acetazolamide, in contrast the BK of SOL was less sensitive to calcium and was resistant to acetazolamide. After 3-14 days HU, in parallel with the slow-to-fast phenotype transition of the fibers, the BK of SOL acquired properties similar to those of FDB. In skeletal muscle, the BK plays muscle-specific roles contributing to the calcium-dependent phenotype determination/adaptation to disuse. The phenotype specificity of acetazolamide has implications for drug-based therapy of neuromuscular disorders associated to disuse.
Tricarico
Domenico
D
Department of Pharmacobiology, Unit of Pharmacology, Faculty of Pharmacy, University of Bari, 70126, via Orabona No. 4, Bari, Italy.
Mele
Antonietta
A
Conte Camerino
Diana
D
D000086:Acetazolamide / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D014893:Weightlessness
D002257:Carbonic Anhydrase Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D000086:Acetazolamide; D002118:Calcium