Extracellular magnesium and calcium reduce myotonia in isolated ClC-1 chloride channel-inhibited human muscle.
BACKGROUND
Experimental myotonia induced in rat muscle by ClC-1 chloride channel-inhibited has been shown to be related inversely to extracellular concentrations of Mg(2+) and Ca(2+) ([Mg(2+) ]o and [Ca(2+) ]o) within physiological ranges. Because this implicates a role for [Mg(2+)]o and [Ca(2+)]o in the variability of symptoms among myotonia congenita patients, we searched for similar effects of [Mg(2+)]o and [Ca(2+)]o on myotonia in human muscle.


METHODS
Bundles of muscle fibers were isolated from abdominal rectus in patients undergoing abdominal surgery. Myotonia was induced by ClC-1 inhibition using 9-anthracene carboxylic acid (9-AC) and was assessed from integrals of force induced by 5-Hz stimulation for 2 seconds.


RESULTS
Myotonia disappeared gradually when [Mg(2+)]o or [Ca(2+)]o were elevated throughout their physiological ranges. These effects of [Mg(2+)]o and [Ca(2+)]o were additive and interchangeable.


CONCLUSIONS
These findings suggest that variations in symptoms in myotonia congenita patients may arise from physiological variations in serum Mg(2+) and Ca(2+).
Department of Biomedicine, Aarhus University, Aarhus, Denmark, Ole Worms Allé 4, 8000, Aarhus C, Denmark.
Martin
M
Skov
Frank Vincenzo
FV
De Paoli
Jesper
J
Lausten
Ole Baekgaard
OB
Nielsen
Thomas Holm
TH
Pedersen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000873:Anthracenes / Q000494:pharmacology; D019540:Area Under Curve; D001703:Biophysics; D002118:Calcium / Q000494:pharmacology*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000473:pathology; D009222:Myotonia / Q000139:chemically induced*
D000873:Anthracenes; C086321:CLC-1 channel; D018118:Chloride Channels; C010030:9-anthroic acid; D008274:Magnesium; D002118:Calcium
ClC-1; extracellular calcium; extracellular magnesium; human muscle; myotonia congenita; phenotypic variation