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The Journal of Neurophysiology Vol. 81 No. 4 April 1999, pp. 1795-1801
Copyright ©1999 by the American Physiological Society
Department of Pharmacology and Therapeutics and Department of Anaesthesia, Faculty of Medicine, The University of British Columbia Vancouver, British Columbia V6T 1Z3, Canada
Ries, Craig R. and
Ernest Puil.
Mechanism of anesthesia revealed by shunting actions of isoflurane on
thalamocortical neurons. By using thalamic brain slices from
juvenile rats and the whole cell recording technique, we determined the
effects of aqueous applications of the anesthetic isoflurane (IFL) on
tonic and burst firing activities of ventrobasal relay neurons. At
concentrations equivalent to those used for in vivo anesthesia, IFL
induced a hyperpolarization and increased membrane conductance in a
reversible and concentration-dependent manner (ionic mechanism detailed
in companion paper). The increased conductance short-circuited the
effectiveness of depolarizing pulses and was the main cause for
inhibition of tonic firing of action potentials. Despite the
IFL-induced hyperpolarization, which theoretically should have promoted
bursting, the shunt blocked the low-threshold Ca2+ spike
(LTS) and associated burst firing of action potentials as well as the
high-threshold Ca2+ spike (HTS). Increasing the amplitude
of either the depolarizing test pulse or hyperpolarizing prepulse or
increasing the duration of the hyperpolarizing prepulse partially
reversed the blockade of the LTS burst. In voltage-clamp experiments on
the T-type Ca2+ current, which produces the LTS, IFL
decreased the spatial distribution of imposed voltages and hence
impaired the activation of spatially distant T channels. Although IFL
may have increased a dendritic leak conductance or decreased dendritic
Ca2+ currents, the somatic shunt appeared to block
initiation of the LTS and HTS as well as their electrotonic propogation
to the axon hillock. In summary, IFL hyperpolarized thalamocortical
neurons and shunted voltage-dependent Na+ and
Ca2+ currents. Considering the importance of the thalamus
in relaying different sensory modalities (i.e., somatosensation,
audition, and vision) and motor information as well as the
corticothalamocortical loops in mediating consciousness, the shunted
firing activities of thalamocortical neurons would be instrumental for
the production of anesthesia in vivo.
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