Molecular Biology and Ion Channel Biophysics: Their Role in Rational Pharmacological Antiarrhythmic Therapy

摘要: Over the past decade investigators interested in cardiac arrhythmias and mechanism of antiarrhythmic drug action have witnessed a true revolution sophistication basic research tools available to study heart its electrical activity. First, introduction patch clamp technique (Hamill et al. 1981) made it relatively easy record membrane currents single myocytes from variety species, without concern for serious limitations imposed by tissue geometry when voltage clamping multicellular preparations (e. g. spatial temporal nonuniformities, changes electrochemical gradient due ion accumulation depletion within narrow intercellular clefts; Johnson Lieberman 1970). Moreover, ability isolate cells specific, welldefined areas helped clarify ionic basis regional differences potential waveform (Antzelevich 1991) their modification disease (Furukawa 1991; Beuckelmann 1993). Finally, capacity resolve current flow at channel level provided an opportunity obtain direct information about gating process drug-channel interactions that would be difficult, if not impossible, using only measurements total current.