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Effect of tetrodotoxin on the early outward currents in perfused giant axons
228
Abstracts
tetrodotoxin (Tz) . Grundfest points out that a distinction should be made between electrically inexcitabk graded responses, such as generator potentials of sensory neurons which are not affected by Tx and graded electrically excitable electrogenesis which depends on Na+ activation such as the graded transient component of the Ltmulus response which would be expected to be blocked by Tx. Benolken in reply (Science, N. Y. 156, 1771, 1967) agrees that their data do not argue against the generalizations discussed by Grundfest. P.R .
Roms, E. and Arw+a~rea, I. (Facultad de Ciencias, Universidad de Chilq Santiago, Chile). Effect of tetrodotoxin on the early outward currents in perfused giant axons. Proc . natn. Acad. Scl. U.S.A . 57, 1350, 1967. Tetrodotozin (T'x) applied externally to giant axons of Dosidicua gigas blocks the early inward current of Na+ without affecting the later outward current of K+ . When K is the only internal cation theearly outward current carried by K+ is also blocked by Tz . The poison appears specific for the fast conductance mechanism in the membrane responsible for thenormal rising phase of theaction potential, regardless of which particular ion is carrying the current. P.R .
Btavs~tmmv, M. P., Armtaesox, N. C. and Nwx.~xwsttt, T. (Dept. of Physiology, Duke Univ. Med. Center, Durham, North Carolina and the Naval Med. Research Institute, Bethesda, Maryland). Basis of tetrodotozin's selectivity in blockage of squid axons. J. gen. Physiol. 50, 1401, 1967. MOORE, J . W.
At x~tt rations were substituted for Na in the sea water bathing an `artificial node' in a voltage-clamped squid axon . Tetrodotoxin (Tk) in concentrations of 100 to 1SO nM always blocked flow of rations through the early transient channels both inward and outward but never blocked flow of ions using the late steady pathway. Selectivity of Tx appears based on some difference between the early and late conductance pathways . Its apecißcity of action does not appear to depend on the ion involved or the direction of cation flow. P.R .
N~tua~n, T., Axntsxsox, N. C. and Mootea, J. W. (Dept . of Physiology, Duke Univ . Med. Center, Durham, North Carolina). Comparison of tetrodotoxin and procaine in internally perfused squid giant axons. J. gen. Physlol. 50, 1413, 1967.
Ir>~e[tNet.t.Y perfused tetrodotoxin ('I'x) even at oonoentrations up to 10 ~M for 36 min is without effect on the resting potential, the action potential, the early transient ionic current or the late steady state current. TX externally applied in a concentration of 100 nM blocked the action potential and the early transient current in 2-3 min. Internally perfused procaine (1-]0 nM) reversibly blocked the action potential and inhibited both the early transient and late steady state currents to the same extent. Since Tx is probably insoluble in lipids it appears that the control for the flow of sodium ions responsible for the early transient current is located on the outer surface of the nerve membrane . Because of the ability of procaine to penetrate through lipid membranes it is able to block the early and late currents whether applied externally or perfused internally . P.R.
Abstracts
tetrodotoxin (Tz) . Grundfest points out that a distinction should be made between electrically inexcitabk graded responses, such as generator potentials of sensory neurons which are not affected by Tx and graded electrically excitable electrogenesis which depends on Na+ activation such as the graded transient component of the Ltmulus response which would be expected to be blocked by Tx. Benolken in reply (Science, N. Y. 156, 1771, 1967) agrees that their data do not argue against the generalizations discussed by Grundfest. P.R .
Roms, E. and Arw+a~rea, I. (Facultad de Ciencias, Universidad de Chilq Santiago, Chile). Effect of tetrodotoxin on the early outward currents in perfused giant axons. Proc . natn. Acad. Scl. U.S.A . 57, 1350, 1967. Tetrodotozin (T'x) applied externally to giant axons of Dosidicua gigas blocks the early inward current of Na+ without affecting the later outward current of K+ . When K is the only internal cation theearly outward current carried by K+ is also blocked by Tz . The poison appears specific for the fast conductance mechanism in the membrane responsible for thenormal rising phase of theaction potential, regardless of which particular ion is carrying the current. P.R .
Btavs~tmmv, M. P., Armtaesox, N. C. and Nwx.~xwsttt, T. (Dept. of Physiology, Duke Univ. Med. Center, Durham, North Carolina and the Naval Med. Research Institute, Bethesda, Maryland). Basis of tetrodotozin's selectivity in blockage of squid axons. J. gen. Physiol. 50, 1401, 1967. MOORE, J . W.
At x~tt rations were substituted for Na in the sea water bathing an `artificial node' in a voltage-clamped squid axon . Tetrodotoxin (Tk) in concentrations of 100 to 1SO nM always blocked flow of rations through the early transient channels both inward and outward but never blocked flow of ions using the late steady pathway. Selectivity of Tx appears based on some difference between the early and late conductance pathways . Its apecißcity of action does not appear to depend on the ion involved or the direction of cation flow. P.R .
N~tua~n, T., Axntsxsox, N. C. and Mootea, J. W. (Dept . of Physiology, Duke Univ . Med. Center, Durham, North Carolina). Comparison of tetrodotoxin and procaine in internally perfused squid giant axons. J. gen. Physlol. 50, 1413, 1967.
Ir>~e[tNet.t.Y perfused tetrodotoxin ('I'x) even at oonoentrations up to 10 ~M for 36 min is without effect on the resting potential, the action potential, the early transient ionic current or the late steady state current. TX externally applied in a concentration of 100 nM blocked the action potential and the early transient current in 2-3 min. Internally perfused procaine (1-]0 nM) reversibly blocked the action potential and inhibited both the early transient and late steady state currents to the same extent. Since Tx is probably insoluble in lipids it appears that the control for the flow of sodium ions responsible for the early transient current is located on the outer surface of the nerve membrane . Because of the ability of procaine to penetrate through lipid membranes it is able to block the early and late currents whether applied externally or perfused internally . P.R.