Activation of the Contractile Mechanism in Striated Muscle

Abstract

Summary. When a frog's striated muscle (m. sartorius) is immersed in Ringer solution containing 2.5–10 × 10–4 w/v of the free base caffeine tension develops and the muscle contracts. The contracture is graded according to dose and reverses rapidly upon removal of the drug. Higher concentrations of caffeine produce an irreversible contracture. In a muscle immersed in isotonic K2SO4 or KCl solution caffeine produces exactly the same kind of muscle contracture as in a muscle kept in Ringer's fluid. Prolonged soaking (96 hours) of a muscle in isotonic K2SO4 solution does not reduce its responsiveness to caffeine. Local application of caffeine from a micropipette to a muscle fibre produces a localized contracture when the tip of the pipette is at the outer surface of the cell membrane. When the tip is inserted into the fibre no contracture is observed indicating that the caffeine action is confined to the muscle membrane. In concentrations helow 10‐3 w/v caffeine does not alter the resting meinhrane potential of iituscle fibres. Neither does the drug markedly reduce the transverse niuscle iiienibraiie resistance. It is suggested that caffeine at the niuscle membrane starts a process which activates the contractile mechanism in the interior of the fibre. This process is believed to be the same as that activated by the propagated action potential. The nature of the process (or processes) linking the membrane to the contractile elements is unknown hut the present results makes it unlikely that it is an electric current or potential change.

Studies on the micro‐injection of various substances into crab muscle fibres

“…8 Taylor (1953), Axelsson & Thesleff (1958), and Conway & Sakai (1960) showed that the external application of 1-3-5 mm caffeine in Ringer's solution to frog muscle fibres could cause a contraction with little or no accompanying depolarization of the fibre membranes. Caffeine contractions were also obtained with fibres which had been previously depolarized in high-potassium solutions, when such fibres were treated with highpotassium solutions containing caffeine (Axelsson & Thesleff, 1958;Conway & Sakai, 1960 (1958) attempted to apply caffeine internally to the fibres they came to the conclusion that the internal application did not cause contraction.…”

The action of calcium ions on potassium contractures of single muscle fibres

“…The 693 height of contraction is quantitatively related to the ratio [Ca]0 :[Na]l (Wilbrandt & Koller, 1948). (5) Caffeine, added to Ringer's solution, can without depolarization produce contractures in twitch fibres (Axelsson & Thesleff, 1958), but not in the heart (Suzuki, 1962).…”

Calcium-Induced Calcium Release in Skeletal Muscle

“…In the early 1990s, it was found that the Ca 2ϩ -releasing action of IP 3 is also enhanced by Ca 2ϩ (14,69,97), and consequently, in the presence of a constant concentration of IP 3 , an increase in Ca 2ϩ concentration causes a further release of Ca 2ϩ from ER/SR through the IP 3 receptor. Thus the IP 3 receptor system exhibits an apparent CICR (12, 98 -100, 176, 250, 264, 274).…”