Use dependence of sodium current inhibition by tetrodotoxin in rat cardiac muscle: influence of channel state

✍ Scribed by Roland Eickhorn; Jörg Weirich; Daniela Hornung; Hermann Antoni

• Publisher: Springer
• Year: 1990
• Tongue: English
• Weight: 943 KB
• Volume: 416
• Category: Article
• ISSN: 0031-6768
• DOI: 10.1007/bf00370746

✦ Synopsis

Tetrodoxin (TTX) is known to cause a voltageand frequency-dependent inhibition of the rapid inward sodium current (IN,) of cardiac muscle. This effect was studied by means of the loose-patch-clamp method on intact rat papillary muscle. The availability curve of the fast sodium system, determined by variation of the holding potential, is shifted in the presence of TTX (5.5 gmol. 1-1) by 17 mV to more negative potentials. With clamp pulses of 5 ms duration to 0 mV, a frequencydependent reduction oflNa by TTX is found above 0.1 Hz that saturates at about 10 Hz. This frequency-dependent block was further analysed using trains of pulses (10 Hz) of various durations (minimum 50 gs), which allow TTX to equilibrate with channel states reached early during activation. The results show that more than 90% of the frequency-dependent block is attained with pulses of 1 ms duration. An analysis according to the guarded receptor hypothesis reveals that these results are well described by TTX binding to inactivated, activated and probably preactivated channel states.