title: Inositol trisphosphate (InsP3) causes contraction in skeletal muscle only under artificial conditions: evidence that Ca2+ release can result from depolarization of T-tubules.
abstract: It has been proposed that in striated muscle inositol 1,4,5-trisphosphate (InsP3) may serve as a chemical transmitter linking membrane depolarization to Ca(2+)-release from the sarcoplasmic reticulum. Key to that hypothesis of excitation-concentration (EC) coupling was the observation that skinned muscle fibres contract on the application of InsP3. Yet skinned fibres do not always respond in this way, and in our hands intact fibres do not contract when InsP3 (1 microM-1 mM) is microinjected into them. Glycerol-shocked fibres do contract, however, and so do intact fibres that have been depolarized to about -50 mV by increasing [K+]0. These observations and related pharmacological evidence support the hypothesis that InsP3 causes a low-level depolarizing current to cross the T-tubular membrane. This current is sufficient to depolarize the T-tubules to the threshold for contraction only when the tubules are sealed over or when they are already close to the threshold. The InsP3-induced Ca2+ release sometimes observed in skinned muscle fibres and in vesicles derived from junctional sarcoplasmic reticulum probably often results from an action on sealed-over transverse tubules; in such situations it is an artifact of cell disruption. The fact that high concentrations of InsP3 do not cause contraction in normal muscle fibres is strong evidence against the hypothesis that InsP3 plays a central role in EC coupling in skeletal muscle.
authors.affiliation: Department of Pharmacology, Mayo Foundation, Rochester, MN 55905.
authors.forename: J D
authors.initials: JD
authors.lastname: Hannon
authors.forename: N K
authors.initials: NK
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Yandong
authors.forename: J R
authors.initials: JR
authors.lastname: Blinks
mesh_terms: D000331:Aequorin; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005990:Glycerol; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D011896:Rana temporaria; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000331:Aequorin; D015544:Inositol 1,4,5-Trisphosphate; D005990:Glycerol; D011188:Potassium; D002118:Calcium