Distinctly different rates of benzocaine action on sodium channels of Ranvier nodes kept open by chloramine-T and veratridine.
Single myelinated nerve fibres of the frog, Rana esculenta, were voltage clamped in a fast-exchange chamber in the presence of 10 mM TEA to block potassium channels. After treatment with 0.6 mM chloramine-T for 1-4 min a sizeable INa component persisted even during a 14-s depolarizing impulse. Changing the perfusate to Ringer solution + 1 mM benzocaine resulted in a fast reduction (half time ca. 0.06 s) of the persistent INa, comparable to the rate of block of peak INa during a series of short impulses before chloramine-T. In the presence of 60 microM veratridine the peak INa was followed by a slow exponential (tau s) reincrease of inward current, Is, that did not appreciably inactivate. Application of 0.25 mM benzocaine during a 14-s depolarizing impulse caused Is to decrease exponentially with a large time constant, tau on of 4.3 s. Recovery on washout proceeded with tau off = 3.4s. Tau on was little dependent on benzocaine concentration and was 4.5 s on the average in 1 mM. Tau on in 25 microM was insignificantly (15%) larger than in 1 mM if tested on the same fibre. After equilibration in 25 microM, 0.25 mM and 1 microM, Is(t = 14s) was reduced to 0.69, 0.30, and 0.10, respectively, of the value without anaesthetic. Cooling by only 4-5 degrees C reduced Is and much increased tau s. tau on (1 mM benzocaine) increased almost in proportion to tau s. Tail currents during a series of pulses (1.1 s every 2.5 s) were reduced by 0.25 mM benzocaine clearly faster (tau on = 1.3 s) than Is during a long pulse of the same amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001566:Benzocaine / Q000494:pharmacology*; D002700:Chloramines / Q000494:pharmacology*; D007452:Iodates / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D011893:Rana esculenta; D011901:Ranvier's Nodes / Q000187:drug effects / Q000378:metabolism*; D012146:Rest; D012964:Sodium / Q000378:metabolism*; D013997:Time Factors; D014105:Tosyl Compounds; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D002700:Chloramines; D007452:Iodates; D007473:Ion Channels; D014105:Tosyl Compounds; C016300:chloramine-T; D014701:Veratridine; D012964:Sodium; D014702:Veratrine; D001566:Benzocaine