Adult and intact sympathetic neurones maintained in vitro at 37°C were analyzed under two-electrode current- or voltage-clamp conditions in order lo investigate the role of IAHP summation. gAHP was activated by short duration calcium currents; the generated IAHP was recognized as the slow component of the Ca-dependent K current which survives at membrane potentials negative to -40 mV as a small monoexponentially decaying tail current. The neurone discharged only once at the onset of a long-lasting depolarizing step. If IAHP was selectively blocked by 100nM apamin or 0.2-0.5 mM d-tubocurarine, accommodation was abolished and an unusual repetitive firing appeared which linearly rose with injected current amplitude (the slope of the fixing frequency-current relationship averaged 26.2 Hz/nA under these conditions) and proved to be independent of starting membrane potential. Accumulation of lAHP was demonstrated under voltage-clamp conditions when depolarizing steps, each evoking the IAHP, were repeated sufficiently close to one another. Under current-clamp conditions, brief threshold depolarizing current pulses repetitively applied at constant frequency could not elicit, without consistent increase, repetitive action potentials with progressive pulse numbers in the train suggesting that an opposing conductance (up to 11 nS) was accumulating with maintained firing. The threshold depolarizing charge, in fact, increased by a factor of 1.4 at 5 Hz, of 1.8 at 10 Hz and of 2.5 at 20 Hz. This result was qualitatively independent of holding potential. The frequency-dependent spike firing ability was eliminated by pharmacological inhibition of the slow IAHP. The IAHP was significantly activated by a single action potential but it was turned on cumulatively by Ca load during successive action potential discharge. This conductance acted in a self-inhibiting manner to limit further cell excitability.

IAHP SUMMATION CONTROLS THE EXCITABILITY OF THE RAT SYMPATHETIC NEURONE

SACCHI, Oscar;ROSSI, Marialisa;CANELLA, Rita
1994

Abstract

Adult and intact sympathetic neurones maintained in vitro at 37°C were analyzed under two-electrode current- or voltage-clamp conditions in order lo investigate the role of IAHP summation. gAHP was activated by short duration calcium currents; the generated IAHP was recognized as the slow component of the Ca-dependent K current which survives at membrane potentials negative to -40 mV as a small monoexponentially decaying tail current. The neurone discharged only once at the onset of a long-lasting depolarizing step. If IAHP was selectively blocked by 100nM apamin or 0.2-0.5 mM d-tubocurarine, accommodation was abolished and an unusual repetitive firing appeared which linearly rose with injected current amplitude (the slope of the fixing frequency-current relationship averaged 26.2 Hz/nA under these conditions) and proved to be independent of starting membrane potential. Accumulation of lAHP was demonstrated under voltage-clamp conditions when depolarizing steps, each evoking the IAHP, were repeated sufficiently close to one another. Under current-clamp conditions, brief threshold depolarizing current pulses repetitively applied at constant frequency could not elicit, without consistent increase, repetitive action potentials with progressive pulse numbers in the train suggesting that an opposing conductance (up to 11 nS) was accumulating with maintained firing. The threshold depolarizing charge, in fact, increased by a factor of 1.4 at 5 Hz, of 1.8 at 10 Hz and of 2.5 at 20 Hz. This result was qualitatively independent of holding potential. The frequency-dependent spike firing ability was eliminated by pharmacological inhibition of the slow IAHP. The IAHP was significantly activated by a single action potential but it was turned on cumulatively by Ca load during successive action potential discharge. This conductance acted in a self-inhibiting manner to limit further cell excitability.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1585465
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