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SK channels are necessary but not sufficient for denervation-induced hyperexcitability. 2002

David Jacobson, and Paco S Herson, and Torben R Neelands, and James Maylie, and John P Adelman
Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, Oregon, USA.

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.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009121 Muscle Denervation The resection or removal of the innervation of a muscle or muscle tissue. Denervation, Muscle,Denervations, Muscle,Muscle Denervations
D009135 Muscular Diseases Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE. Muscle Disorders,Myopathies,Myopathic Conditions,Muscle Disorder,Muscular Disease,Myopathic Condition,Myopathy
D004576 Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Electromyogram,Surface Electromyography,Electromyograms,Electromyographies,Electromyographies, Surface,Electromyography, Surface,Surface Electromyographies
D005207 Fasciculation Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations may be visualized as a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of MOTOR NEURON DISEASE or PERIPHERAL NERVOUS SYSTEM DISEASES. (Adams et al., Principles of Neurology, 6th ed, p1294) Fasciculation, Benign,Fasciculation, Muscular,Fasciculation, Skeletal Muscle,Fasciculation, Tongue,Benign Fasciculation,Benign Fasciculations,Fasciculations,Fasciculations, Benign,Fasciculations, Muscular,Fasciculations, Skeletal Muscle,Fasciculations, Tongue,Muscle Fasciculation, Skeletal,Muscle Fasciculations, Skeletal,Muscular Fasciculation,Muscular Fasciculations,Skeletal Muscle Fasciculation,Skeletal Muscle Fasciculations,Tongue Fasciculation,Tongue Fasciculations
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015221 Potassium Channels Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits. Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel

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