title: Alterations in calcium homeostasis reduce membrane excitability in amphibian skeletal muscle.
abstract: The effects of alterations in intracellular calcium homeostasis on surface membrane excitability were investigated in resting Rana temporaria sartorius muscle. This was prompted by initial results from a fatiguing stimulation protocol study that demonstrated a fibre subpopulation in which action potential generation in response to a standard 1.5 V electrical stimulus failed despite mean membrane potentials [E (m), -69+/-2.3 mV (n=14)] compatible with spike firing in a control set of quiescent muscle fibres. Intracellular micro-electrode recordings showed a similar reversible loss of excitability, attributable to an increased threshold, despite only small (7.1+/-1.8 mV) positive changes in E (m) after approximately 60-min exposures to nominally 0 Ca(2+) Ringer solutions in which Ca(2+) was replaced by Mg(2+). This effect was not reproduced by addition of Mg(2+) to the Ringer solution and persisted under conditions of Cl(-) deprivation. The effects of three pharmacological agents, cyclopiazonic acid (CPA), caffeine and 4-chloro-m-cresol (4-CmC), each known to deplete store Ca(2+) and increase cytosolic Ca(2+) through contrasting mechanisms without influencing E (m), were then investigated. All three agents produced a more rapid, but nevertheless still reversible, loss of membrane excitability than in 0 Ca(2+) Ringer solution alone. This reduction in membrane excitability persisted in fibres studied in solutions containing a normal [Ca(2+)] following prior depletion of store Ca(2+) using CPA- and 4-CmC-containing solutions. These novel findings suggest that sarcoplasmic reticulum Ca(2+) content profoundly influences surface membrane excitability, thereby providing a potential mechanism by which spike firing fails in well-polarised fibres during fatigue.
authors.affiliation: Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, UK. jau20@cam.ac.uk
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Usher-Smith
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: James A
authors.initials: JA
authors.lastname: Fraser
authors.forename: Christopher L-H
authors.initials: CL
authors.lastname: Huang
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D007552:Isotonic Solutions; D018763:Muscle Fatigue / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011896:Rana temporaria; D000077331:Ringer's Solution
chemical_list: D007552:Isotonic Solutions; D000077331:Ringer's Solution; D002118:Calcium