PMID- 11903131 OWN - NLM STAT- MEDLINE DCOM- 20020605 LR - 20191210 IS - 0001-6772 (Print) IS - 0001-6772 (Linking) VI - 173 IP - 4 DP - 2001 Dec TI - Cyclopiazonic acid and thapsigargin reduce Ca2+ influx in frog skeletal muscle fibres as a result of Ca2+ store depletion. PG - 391-9 AB - We have investigated the influence of the sarcoplasmic reticulum (SR) Ca2+ content on the retrograde control of skeletal muscle L-type Ca2+ channels activity by ryanodine receptors (RyR). The effects of cyclopiazonic acid (CPA) and thapsigargin (TG), two structurally unrelated inhibitors of SR Ca(2+)-adenosine triphosphatase (ATPase), were examined on the SR Ca2+ content, the calcium current and contraction in single frog semitendinosus fibres using the double mannitol-gap technique. At moderate concentrations that only partially inhibited Ca2+ sequestration by the SR, CPA (2-4 microM) induces a concentration dependent depression of contraction and Ca2+ current amplitudes. When Ba2+ is the charge carrier, the inward current is not changed by CPA suggesting that this Ca(2+)-pump inhibitor does not directly affect dihydropyridine Ca2+ channels. Similar effects were obtained with TG (1-5 microM). Changes in Ca2+ currents and contraction were accompanied by a reduced Ca2+ loading of the SR. We attribute the modulation of the Ca2+ current to the selective inhibition of the SR Ca2+ ATPase, resulting in a decreased Ca2+ release and thereby a reduced activation of calcium inward currents. This is therefore taken to represent a calcium release-dependent modulation of skeletal muscle L-type Ca2+ channels. FAU - Meme, W AU - Meme W AD - Developpement et Physiologie des Structures Contractiles, CNRS UMR 6018, Faculte des Sciences et des Techniques, Nantes, France. FAU - Leoty, C AU - Leoty C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Acta Physiol Scand JT - Acta physiologica Scandinavica JID - 0370362 RN - 0 (Calcium Channels, L-Type) RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 24GP945V5T (Barium) RN - 67526-95-8 (Thapsigargin) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) RN - X9TLY4580Z (cyclopiazonic acid) SB - IM MH - Animals MH - Barium/pharmacokinetics MH - Calcium/*metabolism MH - Calcium Channels, L-Type/metabolism MH - Calcium-Transporting ATPases/metabolism MH - Enzyme Inhibitors/*pharmacology MH - In Vitro Techniques MH - Indoles/*pharmacology MH - Membrane Potentials/drug effects/physiology MH - Muscle Contraction/physiology MH - Muscle Fibers, Skeletal/drug effects/*metabolism MH - Muscle, Skeletal/cytology/physiology MH - Patch-Clamp Techniques MH - Rana esculenta MH - Sarcoplasmic Reticulum/metabolism MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases MH - Thapsigargin/*pharmacology EDAT- 2002/03/21 10:00 MHDA- 2002/06/06 10:01 CRDT- 2002/03/21 10:00 PHST- 2002/03/21 10:00 [pubmed] PHST- 2002/06/06 10:01 [medline] PHST- 2002/03/21 10:00 [entrez] AID - 918 [pii] AID - 10.1046/j.1365-201X.2001.00918.x [doi] PST - ppublish SO - Acta Physiol Scand. 2001 Dec;173(4):391-9. doi: 10.1046/j.1365-201X.2001.00918.x.