Studies on the Mechanism of Action of D 600 on Isolated Myocytes
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Local anaesthetics block the sodium channel mainly in the activated open state. The block depends on the frequency of the activations and on the membrane potential. They reach the receptor in the sodium channel from the cytoplasm side of the membrane and act in the charged form (Cahalan et al. 1980; Hille 1977 a, b; Strichartz 1973). There are many similarities between this block and the calcium channel block by D 600. For example, in recent years we have shown in voltage clamp studies that D 600 binds preferentially to the open, activated channel, i. e. the cell must be activated for the block to occur. The more frequently the channels are activated the more powerful the block (use dependency). On the other hand, D 600 “dissociates” from the receptor in diastole, i. e. the block is reversed, the degree of this reversal depending on the duration of diastole (McDonald et al. 1980; Pelzer et al. 1982; Trautwein et al. 1983).
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- Cahalan M, Shapiro BI, Almers W (1980) Relationship between inactivation of sodium channels and block by quarternary derivatives of local anesthetics and other compounds. In: Fink BR (ed) Progress in anesthesiology, vol 2. Molecular mechanisms of anesthesia. Raven, New York, p 17–33Google Scholar
- Trautwein W, Pelzer D, McDonald TF (1983) Interval- and voltagedependent effects of the calcium channel blocking agents D600 and AQA39 on mammalian ventricular muscle. Circ Res in pressGoogle Scholar