CA2-MUSCLES( RELEASE CHANNELS IN RAT DENERVATED SKELETAL)

Sarcoplasmic reticulum (SR) Ca2+ release channel-ryanodine receptors ( RYR1) from rat fast-twitch skeletal muscle were studied by incorporati ng heavy sarcoplasmic reticulum membranes into a lipid bilayer. Channe ls from normal and denervated muscles had the same conductance as that reported for rabbits (about 500 pS) in 250:250 mM cis:trans caesium m ethanesulphonate. Caffeine (0.1 mM) induced a larger increase in the o pen probability (P-o) in denervated than in normal channels. The caffe ine effect was caused by changes in mean open and burst time distribut ions. Longer opening and burst events were detected in the presence of caffeine. High caffeine concentrations (4 mM) gave similar results in channels from normal and denervated muscles. In denervated muscle, un like intact muscle, the Ca2+ release channel was not activated at mill imolar Ca2+ concentrations; this is similar to the cardiac isoform of the channel. Maximal channel activation was shifted to higher Ca2+ con centrations (pCa 4) and the channel remained activated at millimolar C a2+ concentrations. The main effect of millimolar Ca2+ concentrations upon Ca2+ release channels from denervated muscles was an increase in the mean open time, with a concomitant increment of the mean burst dur ation. Alterations in channel gating properties in calcium and caffein e account for changes in the mechanical response after skeletal muscle denervation.