English to Russian Science Biology (-tech,-chem,micro-) neurobiology

Figure 4.

Voltage-dependent and frequency-dependent inhibition of voltage-gated Na+ channels by Na+ channel blockers (A) Inhibition of Na+ currents by phenytoin is dependent on membrane holding potential. The top traces show currents evoked by depolarisation to 0 mV, with control (a standard physiological saline solution) and with 50 M phenytoin. In each of the four pairs of current traces, the larger trace is the control. The traces on the left were elicited from a holding potential of 130 mV, whereas the traces on the right were from a holding potential of 65 mV. The control current at 65 mV is smaller, due to greater inactivation induced by the more depolarised holding potential. Moreover, phenytoin is a much more effective blocker at the more depolarised holding potential. This is more evident in the bottom traces, in which the amplitudes have been scaled so that the control currents are the same size. (B) Phenytoin block builds up during repetitive channel activation. The graph shows normalised current amplitudes of whole-cell Na+ currents over the course of depolarising pulses to 0 mV, from a holding potential of 85 mV, applied at 2 Hz. Red dots indicate discrete measurements. Dashed line indicates a baseline to monitor decline in amplitude. (C) Voltage-dependent and frequency-dependent inhibition of Na+ channels by phenytoin and other antiepileptic or local anaesthetic drugs with a similar mode of action (green diamond) are qualitatively explained by a modulated receptor model. In this model, the drug binds with higher affinity to inactivated channel states than to resting channel states. Biophysical and molecular data suggest that the modulated receptor site is within the inner vestibule of the ion-conducting pore.

https://www.semanticscholar.org/paper/Voltage-gated-sodium-c...

https://pubmed.ncbi.nlm.nih.gov/20298965/