Altered Na+ channel activity and reduced Cl- conductance cause hyperexcitability in recessive generalized myotonia (Becker).
Intact muscle fibers or resealed fiber segments from 7 patients with recessive generalized myotonia were studied in vitro. All fibers had normal resting membrane potentials and normal resting [Ca2+]i several hours after removal. Contractions were characterized by slowed relaxation which was due to electrical after-activity. Often spontaneous depolarizations were recorded intracellularly. In all fibers, the steady state voltage-current relationship was abnormal, due to a reduced Cl- conductance. However, this conductance ranged from 0% to 66% of the total membrane conductance, whereas, in normal muscle, it was 80%. Theoretically, myotonic after-discharges would not appear until the Cl- conductance is below 20%. Thus, the membrane hyperexcitability must be due to another defect, at least in the preparations in which the Cl- conductance was only slightly reduced. In all patches from all patients investigated with the patch clamp technique, we observed reopenings of the Na+ channels throughout depolarizing pulses (such behavior was absent in normal muscle). If a patch was polarized to potentials less negative than the resting potential, the duration of the reopenings increased. We conclude that a combination of reduced Cl- conductance and the reopenings of Na+ channels underlie the electrical after-activity in recessive generalized myotonia.
Franke
C
C
Neurologische Klinik, Technischen Universität München, FRG.
Iaizzo
P A
PA
Hatt
H
H
Spittelmeister
W
W
Ricker
K
K
Lehmann-Horn
F
F
D002712:Chlorides / Q000378:metabolism*; D004576:Electromyography; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D009132:Muscles / Q000378:metabolism* / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics / Q000503:physiopathology*; D015222:Sodium Channels / Q000378:metabolism*
D002712:Chlorides; D007473:Ion Channels; D015222:Sodium Channels