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D J Adams

Publications and source records attributed to D J Adams.

8 recordsLinked to original sources

Ionic currents in response to membrane depolarization in an Aplysia neurone.

1. Action potentials recorded in the soma of R15 neurones in the abdominal ganglia of Aplysia juliana were not suppressed by selective inhibition of either Na or Ca conductance alone. It was necessary to block both conductances to suppress action potentials. 2. Membrane currents generated by step depolarizations of the soma consisted of early transient and delayed steady-state currents. The early transient current could have one or two components depending on the activating depolarization. 3. The early more rapid component had a reversal potential at +54 mV and the reversal potential changed with extracellular Na concentration in accord with the Nernst equation. It was blocked by substitution of impermeant cations for Na, by TTX and by internal injections of Zn. It was concluded that this component was normally a Na current. 4. The later slower component of the transient current had a reversal potential at about +65 mV and the reversal potential changed with extracellular Ca concentration is accord with the Nernst equation. It was blocked by substitution of Mg for Ca or addition of Mn, Co, Ni or verapamil to the extracellular solution. It was concluded that this component was normally a Ca current. 5. Na and Ca currents were generated at different threshold potentials, Na currents first appearing at about -20 mV and Ca currents at -5 to 0 mV. 6. The time-to-peak of both Na and Ca currents was affected by the holding potential, by the amplitude of the activating depolarization, by temperature and by divalent ion concentration. 7. The peak Na and Ca conductances both increased sigmoidally with increasing depolarization, the maximum Na conductance of 10--15 microS being approximately twice the maximum Ca conductance. Peak conductances for Na and Ca reached half-maximum at -8 and +3 mV, respectively. 8. The amplitude of the delayed steady-state current could be varied by changing the extracellular K+ ion concentration or by adding tetraethylammonium to the extracellular solution. The reversal potential for 'tail currents' was -67 mV and shifted 18 mV when the extracellular K concentration was doubled. It was concluded that the delayed steady-state current was K current. 9. With prolonged depolarizations, K current decayed with a time constant of the order of 1 sec. Peak K conductance increased with increasing depolarization with the half-maximum occurring at a potential more positive than +20 mV. The maximum rate of fractional activation of K conductance was independent of the amplitude of the clamp step.

Action Potentials

Characteristics of sodium and calcium conductance changes produced by membrane depolarization in an Aplysia neurone.

1. The time course and voltage dependence of Na and Ca conductance changes produced by depolarization of the soma of the neurone R15 in the abdominal ganglion of Aplysia juliana were examined at temperatures of 10--14 degrees C. 2. During a maintained depolarization, Na currents turned on then decayed (inactivated). Inactivation was exponential with time constant tauh. Activation (after correction for inactivation) was reasonably well described by the expression G'Na(t) = G'Na (infinity) (1 - exp [-t/taum])3 over a wide range of potentials. 3. taum and tauh were both voltage dependent. In the range -20 to +40 mV, taum varied from 5 to 0.5 msec and tauh from 25 to 8 msec (13.5 degrees C). Steady-state Na conductance (corrected for inactivation) was voltage dependent also, increasing sigmoidally with depolarization to a maximum of 25--30 muS at +10 to +20 mV. Half-maximal Na conductance occurred at a membrane potential of -8 mV and from -15 to -5 mV, a 5 mV change in membrane potential produced an e-fold change in steady-state Na conductance. 4. Steady-state inactivation of Na conductance (hNa(infinity)) was voltage dependent with half-inactivation occurring at a membrane potential of -32 mV. Recovery from Na inactivation followed an exponential time course with a voltage-dependent time constant. 5. During a maintained depolarization Ca currents activated then decayed (inactivated) more slowly than Na currents. The decay was exponential with time constant tauH. The decay of Ca current was not an artifact porduced by an outward current. The amplitude of calcium tail currents, produced by voltage steps back to epsilonK at different times during the decay of ICa, decayed also with a time constant close to tauH. 6. Ca conductance (after correction for inactivation) could be described approximately by the expression G'Ca(t) = G'Ca(infinity) (1 - exp [-t/tauM])p but it was necessary to vary p from 1 to 2 at different potentials. No value of p gave as good a fit to this model as that obtained for Na currents. 7. taum and tauH were voltage dependent. In the range of potentials from 0 to +60 mV, tauM varied from 9 to 5 msec and tauH from 300 to 50 msec (13.5 degrees C). Steady-state Ca conductance (corrected for inactivation) was voltage dependent also, increasing sigmoidally with depolarization to a maximum of 10--15 muS at +30 to +40 mV. Half-maximal Ca conductance occurred at a membrane potential of +12 mV, and from +10 to +20 mV a 6 mV change in membrane potential produced an e-fold change in Ca conductance. 8. Steady-state inactivation of Ca conductance (hCa(infinity)) varied with holding potential (VH). Half-inactivation occurred with depolarization to -20 mV. At potentials more negative than -40 mV, hCa(infinity) was less than at -40 mV, i.e. hyperpolarization produced Ca 'inactivation'. 9...

Animals

Sodium and calcium gating currents in an Aplysia neurone.

1. Currents generated by depolarizing the hyperpolarizing voltage pulses were recorded at temperatures of 4--12 degrees C in the voltage-clamped soma of R15 in aplysia abdominal ganglia exposed to solutions which suppressed ionic currents. 2. Subtraction of linear capacitive and leakage currents from current generated by voltage pulses to levels more positive than -20mV revealed non-linear transient outward displacement currents at the onset of the clamp step (on-current) and transient inward displacement currents after the membrane potential returned to the holding potential (off-current). Only on-currents were studied. 3. Pulses to membrane potentials of -20 to 0 mV generated a displacement current with rapid onset and exponential decay. At membrane potentials more positive than o mV a second displacement current with a much slower onset and slower exponential decay was seen. Because the different threshold potentials for the two displacement currents were close to the different threshold potentials for Na and Ca ion currents, the two displacement currents were called Na and Ca 'gating' currents. 4. The amount of charge transfer during Ca gating currents increased sigmoidally with increasing depolarization, reaching a maximum at +30 to +40 mV. Half-maximum charge transfer occurred at +15 mV. 5. Total charge movement during Ca gating currents was maximal with holding potentials of -30 to -40 mV. More positive or more negative holding potentials produced a decrease in charge movement. 6. The time course of the gating currents, but not the total charge displaced, was very sensitive to temperature. The time constant of decay of Ca gating currents had a Q10 of about 3, whereas the total amount of charge displaced had a Q10 of 1.2. 7. The charge transfer during both Na and Ca gating currents and the amplitude of Na and Ca (but not K) ionic currents were reduced in solutions containing 1 mm-n-octanol.

Animals

Sodium valproate in the treatment of intractable seizure disorders: a clinical and electroencephalographic study.

A 12-week study of clinical response, EEG changes and serum antiepileptic drug (AED) levels using sodium valproate (VAL) was undertaken. The study showed that VAL is a powerful adjunct in the treatment of intractable epilepsy. It was most effective in patients with generalized seizures, but no seizure type was totally resistant. No serious adverse effects were encountered; nausea was easily overcome by readjusting the drug dosage. In most cases the only EEG change was decrease of epileptiform activity, and this correlated well with decreased frequency of clinical seizures. These two features in turn were most often seen with a serum VAL level of 40 microgram per milliliter or greater. Intoxication with VAL was accompanied by marked slowing of the background rhythms, but no increase in beta activity. Other modifications of the EEG were probably due to changes in the plasma levels of other drugs. Interactions between VAL and conventional antiepileptic drugs occur, so that serum concentrations of all drugs must be monitored in patients receiving VAL.

Adult