Skeletal muscle and small-conductance calcium-activated potassium channels

Skeletal muscle becomes hyperexcitable following denervation and when cultu red in the absence of nerve cells. In these circumstances, the bee venom pe ptide toxin apamin, a blocker of small-conductance calcium-activated potass ium (SK) channels, dramatically reduces the hyperexcitability, In this repo rt, we show that SK3 channels are expressed in denervated skeletal muscle a nd in L6 cells, Action potentials evoked from normal innervated rat skeleta l muscle did not exhibit an afterhyperpolarization, indicating a lack of SK channel activity; very low levels of apamin binding sites, SK3 protein, or SK3 mRNA were present. However, denervation resulted in apamin-sensitive a fterhyperpolarizations and increased apamin binding sites, SK3 protein, and SK3 mRNA. Cultured rat L6 myoblasts and differentiated L6 myotubes contain ed similar levels of SK3 mRNA, although apamin-sensitive SK currents and ap amin binding sites were detected only following myotube differentiation. Th erefore, different molecular mechanisms govern SK3 expression levels in den ervated muscle compared with muscle cells differentiated in culture. (C) 19 99 John Wiley & Sons, Inc.