CA2-MUSCLE FIBERS( CHANNEL ANTAGONISTS ENHANCE TENSION IN SKINNED SKELETAL AND HEART)

Striated muscle fibres, both skeletal and cardiac of different species including human, skinned by freeze-drying, were activated in solution s strongly buffered for Ca2+. The single fibres were immersed in solut ions with different [Ca2+]. Sarcomere length was set and controlled by laser diffraction. Fibre type was determined by Sr2+ activation. The relation between the negative logarithm of the Ca2+ concentration and the normalized tension, the Ca2+ sensitivity curve, was investigated. The effect on the contractile machinery of three different Ca2+ channe l antagonists (verapamil, diltiazem and nifedipine) in a therapeutic c oncentration (10(-6) M) was investigated. The possible effects on the Ca2+ sensitivity curve were quantified by: (1) the change in maximal t ension developed at pCa(2+)=4.4; (2) the change in pCa(2+) value at wh ich 50% of the tension induced at pCa(2+)=4.4; (3) the steepness of th e Ca2+ sensitivity curve in this point. The three drugs tested, at a t herapeutic concentration of 1 mu M, all enhanced maximal induced tensi on by respectively 25, 20 and 7%. The sarcomere length dependency of t he effect proved to be dependent upon the drug, but also slightly on f ibre type (skeletal or cardiac), or on species. It is concluded that t he drug influences the cooperativity of the two different types of bin ding sites on troponin-C (low- and high-affinity sites). Tension enhan cement was due to increased stiffness of the actin-myosin interaction site.