Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.
Bottom Line: However, in Ci-VSP-expressing fibers challenged by 5-s-long depolarizing pulses, the Ca(2+) level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV.Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers, and that VSP-induced depletion of PtdIns(4,5)P2 impairs voltage-activated Ca(2+) release from the SR.Because Ca(2+) release is thought to be independent from InsP3 signaling, the effect likely results from an interaction between PtdIns(4,5)P2 and a protein partner of the E-C coupling machinery.
Affiliation: Centre National de la Recherche Scientifique UMR 5534, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire, 69100 Villeurbanne, France.Show MeSH
Related in: MedlinePlus
License 1 - License 2
Mentions: The above data are consistent with the possibility that activation of VSP in the transverse tubule membrane affects Ca2+ release. We examined whether the function of Cav1.1, which acts both as voltage sensor for E-C coupling and as voltage-dependent Ca2+ channel, would be affected after VSP activation. For this, we measured the Ca2+ current in fibers challenged by a double-pulse protocol. The membrane voltage was first stepped from −80 to 20 mV for 5 s (prepulse) and then, after a 1-s delay, from −80 to 20 mV for 1 s (test pulse). The double pulse was then applied with the prepulse to 120 mV to activate the VSP and then again with the prepulse to 20 mV as a bracketing control. In each fiber, the whole protocol was repeated with a 2-s and with a 5-s interval between the prepulse and the test pulse. Corresponding membrane current traces from a Ci-VSP–expressing fiber are shown in Fig. 8 (A–C). In each panel, the two membrane current records with the prepulse to 20 mV are in black, and the record with the prepulse to 120 mV is in red.
Affiliation: Centre National de la Recherche Scientifique UMR 5534, Université Lyon 1, Centre de Génétique et de Physiologie Moléculaire et Cellulaire, 69100 Villeurbanne, France.