Ciliary neurotrophic factor promotes inactivation of muscle Ca2+ channels via PKC.
The actions of the ciliary neurotrophic factor (CNTF) were assessed on adult mouse skeletal muscle L-type Ca2+ currents and on Ca2+ release from sarcoplasmic reticulum. Currents were measured with the whole cell patch clamp technique. Ca2+ signals in response to single action potentials were recorded with Fluo3-AM. CNTF (20 ng/ml) reversibly reduced the amplitude of Ca2+ channel currents by 50% within 15 min. In addition, CNTF greatly increased the rate of inactivation during depolarizing pulses and shifted the steady state inactivation curve by -12 mV. The effects of CNTF were mimicked by the PKC activator PMA and prevented by the PKC-inhibitor chelerythrine. In contrast to the effects on the Ca2+ conductance, charge movement and Ca2+ signals remained unaffected by CNTF. These results suggest that CNTF can rapidly decrease muscle Ca2+ channel currents by promoting inactivation, probably through an intracellular PKC-dependent mechanism.
Zaldivar
Daniel
D
Departmento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N., México, DF 07360, Mexico.
García
María C
MC
Sánchez
Jorge A
JA
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002413:Cations, Divalent / Q000737:chemistry; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*
D015220:Calcium Channels; D002413:Cations, Divalent; D020934:Ciliary Neurotrophic Factor; D011493:Protein Kinase C; D002118:Calcium