SK channels are necessary but not sufficient for denervation-induced hyperexcitability.
Skeletal muscle hyperexcitability is characteristically associated with denervation. Expression of SK3, a small conductance Ca(2+)-activated K(+) channel (SK channel) in skeletal muscle is induced by denervation, and direct application of apamin, a peptide blocker of SK channels, dramatically reduces hyperexcitability. To investigate the role of SK3 channels in denervation- induced hyperexcitability, SK3 expression was manipulated using a transgenic mouse that harbors a tetracycline-regulated SK3 gene. Electromyographic (EMG) recordings from anterior tibial (AT) muscle showed that denervated muscle from transgenic or wild-type animals had equivalent hyperexcitability that was blocked by apamin. In contrast, denervated skeletal muscle from SK3tTA mice lacking SK3 channels showed little or no hyperexcitability, similar to results from wild-type innervated skeletal muscle. However, innervated skeletal muscle from SK3tTA mice containing SK3 channels did not show hyperexcitability. The results demonstrate that SK3 channels are necessary but not sufficient for denervation-induced skeletal muscle hyperexcitability.
Jacobson
David
D
Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, Oregon, USA.
Herson
Paco S
PS
Neelands
Torben R
TR
Maylie
James
J
Adelman
John P
JP
D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D004576:Electromyography; D005207:Fasciculation / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics; D009121:Muscle Denervation / Q000009:adverse effects*; D018482:Muscle, Skeletal / Q000294:innervation* / Q000503:physiopathology*; D009135:Muscular Diseases / Q000503:physiopathology*; D015221:Potassium Channels / Q000172:deficiency* / Q000235:genetics; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels
C496900:Kcnn3 protein, mouse; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels