Ca2+ channel antagonists enhance tension in skinned skeletal and heart muscle fibres.

作者: Piet Schiereck , Evert De Beer , Bas Van Heijst , Paul Janssen , Alexandra Van Andel

DOI: 10.1016/0014-2999(93)90528-P

关键词: DiltiazemSarcomereBiophysicsMechanism of actionVerapamilNifedipineChemistryContractilityCooperativityInternal medicineMuscle contractionEndocrinology

摘要: Abstract Striated muscle fibres, both skeletal and cardiac of different species including human, skinned by freeze-drying, were activated in solutions strongly buffered for Ca 2+ . The single fibres immersed with [Ca ]. Sarcomere length was set controlled laser diffraction. Fibre type determined Sr activation. relation between the negative logarithm concentration normalized tension, sensitivity curve, investigated. effect on contractile machinery three channel antagonists (verapamil, diltiazem nifedipine) a therapeutic (10 −6 M) possible effects curve quantified by: (1) change maximal tension developed at pCa = 4.4; (2) value which 50% induced (3) steepness this point. drugs tested, 1 μM, all enhanced respectively 25, 20 7%. sarcomere dependency proved to be dependent upon drug, but also slightly fibre (skeletal or cardiac), species. It is concluded that drug influences cooperativity two types binding sites troponin-C (low- high-affinity sites). Tension enhancement due increased stiffness actin-myosin interaction site.

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