The effect of caffeine on excitation-contraction coupling in skeletal and smooth muscle.

1. For cockroach skeletal muscle, 2 mM caffeine considerably lowered the mechanical threshold without affecting the membrane potential. Constractures were induced by 8-10 mM caffeine. 2. In rat ileal smooth muscle, 1-10 mM caffeine inhibited spontaneous contractile behaviour, abolished spike activity and reduced KCl-induced contracture tension. 3. Enhanced spike activity associated with the KCl-induced phasic contraction was abolished by caffeine, the degree of caffeine-induced relaxation being proportional to the concentration employed. These relaxations were not accompanied by membrane hyperpolarization. 4. The present results accord with previous work which has shown that caffeine increases myoplasmic free calcium in the skeletal muscle and lowers it in the smooth muscle. It is suggested that caffiene releases bound calcium in the former muscle and promotes binding in the latter. 5. It is further suggested that in the smooth muscle caffeine may reduce the membrane permeability to calcium.