Caffeine and length dependence of staircase potentiation in skeletal muscle

Skeletal muscle sensitivity to Ca2+ is greater at long lengths, and this re sults in an optimal length for twitch contractions that is longer than opti mal length for tetanic contractions. Caffeine abolishes this length depende nce of Ca2+ sensitivity. Muscle length (ML) also affects the degree of stai rcase potentiation. Since staircase potentiation is apparently caused by an increased Ca2+ sensitivity of the myofilaments, we tested the hypothesis t hat caffeine depresses the length dependence of staircase potentiation. In situ isometric twitch contractions of rat gastrocnemius muscle before and a fter 10 s of 10-Hz stimulation were analyzed at seven different lengths to evaluate the length dependence of staircase potentiation. In the absence of caffeine, length dependence of Ca2+ sensitivity was observed, and the degr ee of potentiation after 10-Hz stimulation showed a linear decrease with in creased length (DT = 1.47 - 0.05ML, r(2) = 0.95, where DT is developed tens ion). Length dependence of Ca2+ sensitivity was decreased by caffeine when caffeine was administered in amounts estimated to result in 0.5 and 0.75 mM concentrations. Furthermore, the negative slope of the relationship betwee n staircase potentiation and muscle length was diminished at the lower caff eine dose, and the slope was not different from zero after the higher dose (DT = 1.53 - 0.009ML, r(2) = 0.43). Our study shows that length dependence of Ca2+ sensitivity in intact skeletal muscle is diminished by caffeine. Ca ffeine also suppressed the length dependence of staircase potentiation, sug gesting that the mechanism of this length dependence may be closely related to the mechanism for length dependence of Ca2+ sensitivity.