Alterations in calcium homeostasis reduce membrane excitability in amphibian skeletal muscle.
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.
Usher-Smith
Juliet A
JA
Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, UK. jau20@cam.ac.uk
Xu
Wei
W
Fraser
James A
JA
Huang
Christopher L-H
CL
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
D007552:Isotonic Solutions; D000077331:Ringer's Solution; D002118:Calcium