Effects of dantrolene and methylxanthines on the sensory nerve terminal of the frog muscle spindle.

The application of 1.5-4 microM dantrolene decreased the threshold and the current sensitivity of the rhythmic hyperpolarizations that occur during depolarization of the sensory nerve terminal in the frog muscle spindle. The higher concentration provoked spontaneous rhythmic changes even without depolarization. Methylxanthines (5 mM caffeine, theophylline or pentylene-tetrazole) increased the threshold and the sensitivity. Electron microscopic observations of the dantrolene-treated spindles revealed numerous electron-dense deposits associated with the cytoplasmic membrane of the sensory terminals and with mitochondrial membranes. The deposits were found to contain K+ and Ca2+ by energy dispersive X-ray microanalysis. Electron-dense deposits containing Ca2+ were usually observed in the inner capsular space and in the mitochondria of the sensory terminals perfused by normal or high Ca2+ Ringer solutions. They were reduced in number following incubation with methylxanthines. The amplitudes of afferent spikes and the spindle potential were increased by methylxanthines in much the same way as by K+ channel blockers, suggesting that GK of the terminal membrane may be reduced by methylxanthines. We suggest that methylxanthines may modulate the terminal responses both as a K+ channel blocker and by enhancing the release of Ca2+ from a storage site, perhaps in the inner capsular space, whereas dantrolene has the opposite effect.