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Small‐conductance calcium‐activated potassium currents in mouse hyperexcitable denervated skeletal muscle
Author(s) -
Neelands Torben R.,
Herson Paco S.,
Jacobson David,
Adelman John P.,
Maylie James
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0397c.xd
Subject(s) - apamin , depolarization , biophysics , chemistry , current clamp , iberiotoxin , cardiac transient outward potassium current , membrane potential , skeletal muscle , repolarization , reversal potential , potassium channel , patch clamp , voltage clamp , electrophysiology , anatomy , medicine , biology
1 Hyperexcitability in denervated skeletal muscle is associated with the expression of SK3, a small‐conductance Ca 2+ ‐activated K + channel (SK channel). SK currents were examined in dissociated fibres from flexor digitorum brevis (FDB) muscle using the whole‐cell patch clamp configuration. 2 Depolarization activated a K + ‐selective, apamin‐sensitive and iberiotoxin‐insensitive current, detected as a tail current upon repolarization, in fibres from denervated but not innervated muscle. Dialysis of the fibres with 20 m m EGTA in the patch pipette solution eliminated the tail current, consistent with this current reflecting Ca 2+ ‐activated SK channels expressed only in denervated muscle. 3 Activation of SK tail currents depended on the duration of the depolarizing pulse, consistent with a rise in intracellular Ca 2+ due to release from the sarcoplasmic reticulum (SR) and influx through voltage‐gated Ca 2+ channels. 4 The envelope of SK tail currents was diminished by 10 μ m ryanodine for all pulse durations, whereas 2 m m cobalt reduced the SK tail current for pulses greater than 80 ms, demonstrating that Ca 2+ release from the SR during short pulses primarily activated SK channels. 5 In current clamp mode with the resting membrane potential set at −70 mV, denervation decreased the action potential threshold by ∼8 mV. Application of apamin increased the action potential threshold in denervated fibres to that measured in innervated fibres, suggesting that SK channel activity modulates the apparent action potential threshold. 6 These results are consistent with a model in which SK channel activity in the T‐tubules of denervated skeletal muscle causes a local increase in K + concentration that results in hyperexcitability.