Cyclopiazonic acid and thapsigargin reduce Ca 2+ influx in frog skeletal muscle fibres as a result of Ca 2+ store depletion

• Published in: Acta physiologica Scandinavica Vol. 173; no. 4; pp. 391 - 399
• Main Authors: MÊME, W., LÉOTY, C.
• Format: Journal Article
• Language: English
• Published: 01-12-2001
• ISSN: 0001-6772; 1365-201X
• DOI: 10.1046/j.1365-201X.2001.00918.x

We have investigated the influence of the sarcoplasmic reticulum (SR) Ca
2+
content on the retrograde control of skeletal muscle L‐type Ca
2+
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 Ca
2+
content, the calcium current and contraction in single frog semitendinosus fibres using the double mannitol‐gap technique. At moderate concentrations that only partially inhibited Ca
2+
sequestration by the SR, CPA (2–4 
μ
M
) induces a concentration dependent depression of contraction and Ca
2+
current amplitudes. When Ba
2+
is the charge carrier, the inward current is not changed by CPA suggesting that this Ca
2+
‐pump inhibitor does not directly affect dihydropyridine Ca
2+
channels. Similar effects were obtained with TG (1–5 μ
M
). Changes in Ca
2+
currents and contraction were accompanied by a reduced Ca
2+
loading of the SR. We attribute the modulation of the Ca
2+
current to the selective inhibition of the SR Ca
2+
ATPase, resulting in a decreased Ca
2+
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 Ca
2+
channels.