Colchicine alters apamin receptors, electrical activity, and skeletal muscle relaxation

Abstract

A low conductance calcium-activated K+ channel is thought to regulate the rate of firing of several excitable cells. In skeletal muscle the expression of this channel is under nerve control. Previously, we reported that axonal flow blockade of rat nerves, induced by colchicine, caused a transient increase in muscle apamin receptors, determined by 125I-apamin binding to membrane fractions. The increase in apamin receptors was correlated with repetitive discharges resembling myotonic potentials in the electromyogram, that were blockable by apamin. Here we show that the increase in muscle apamin receptors and the alteration of the electromyogram are followed closely by a slowing of the twitch relaxation, that in turn, is decreased by apamin. Furthermore, the presence of myotonic-like alterations in the electromyogram and a slowing of muscle relaxation when muscle apamin receptors are increased suggests that these channels may participate, among other factors, in the generation of some kinds of myotonia.

Skeletal muscle and small-conductance calcium-activated potassium channels

“…Application of the bee venom peptide toxin apamin, a blocker of SK channels, dramatically reduces the hyperexcitability of denervated muscle, 44 implicating SK channels in the genesis of the hyperexcitability. The experiments presented here investigated the molecular basis for SK channel-mediated skeletal muscle hyperexcitability following denervation or in cultured muscle cells.…”

“…Although the molecular basis for the hyperexcitability is not yet understood, these conditions share an important property: the tissue contains receptors for the bee venom peptide toxin apamin, a blocker of small-conductance calciumactivated potassium (SK) channels, and apamin application reduces or abolishes the hyperexcitability, 10,38,44 suggesting that SK channels are central to the genesis of the hyperexcitability.…”

The denervated muscle: facts and hypotheses. A historical review

“…It was indeed observed that following axoplasmic Xow blockade, as well as nerve section, the number of apaminesensitive calcium activated K + channels-whose level is negligible in innervated muscles-increases, with an increase of muscle Wber excitability which might be related to Wbrillation activity (Behrens and Vergara 1992;Ramirez et al 1996;Vergara et al 1993). Direct application of colchicine to the muscle did not alter the channel expression, while histological examination of the nerve showed no signs of nerve lesions (Behrens and Vergara 1992).…”

“…ThesleV and Ward (1975) suggested that normal levels of calcium ions in denervated muscle are less eVective as membrane stabilizing agents, which should favor membrane spontaneous activity, and a role of cytosolic calcium in the genesis of Wbrillation has been proposed by Brodie (1966) and Izumi et al (1998). The occurrence of Wbrillation has also been related to the increase of a particular kind of low conductance, Ca 2+ -activated K + channels after denervation, with a resulting increase of excitability of muscle Wber membrane (Vergara et al 1993) (see also "Extrajunctional membrane properties" section). Quite recently, in light of the results obtained with in vitro myogenesis, it was proposed that Wbrillation is related to the autocrine activation of AChRs in muscle Wber membrane (Bandi et al 2005).…”

Disruption of axoplasmic transport induces mechanical sensitivity in intact rat C‐fibre nociceptor axons

“…At low doses, their topical application can effectively block axoplasmic transport in both myelinated and unmyelinated axons without causing axonal damage (< 10 m m for colchicine: Jackson & Diamond, 1977; Tiedt et al . 1977; Vergara et al . 1993; Kingery et al .…”