Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a
K + conductance.
Cox, Charles L., John R. Huguenard and David A. Prince.
Department of Neurology and Neurological Sciences, Room M016, Stanford
University Medical Center, Stanford, CA 94305.
APStracts 2:0137N, 1995.
SUMMARY AND CONCLUSIONS
1. The thalamic reticular nucleus (nRt) is innervated by cholecystokinin
(CCK)-containing neurons and contains CCK binding sites. We used tight-seal,
whole cell recording techniques with in vitro rat thalamic slices to
investigate the action of CCK on neurons in nRt and ventrobasal thalamus (VB).
2. Brief applications of the CCK agonist, cholecystokinin (26-33) sulfated,
(CCK8S), evoked prolonged spike discharges in nRt neurons, but had no direct
effects on VB neuron activity. This selective excitatory action of CCK8S in
nRt resulted from a long-lasting membrane depolarization (2-10 min.)
associated with an increased input resistance. Voltage clamp recordings
revealed that CCK8S reduced membrane conductance by 0.6 to 3.8 nS, which
amounted to 5 to 54% of the resting conductance of these neurons. 3. The
conductance blocked by CCK8S was linear over the range of -50 to -100 mV, and
reversed near E K . Modifications of extracellular [K + ] altered the reversal
potential of the conductance as predicted by the Nernst equation. The K +
channel blocker, Cs + , applied either intracellularly or combined intra- and
extra-cellularly, blocked the response to CCK8S. 4. The CCK8S-induced
depolarization persisted following suppression of synaptic transmission by
either tetrodotoxin or a low Ca 2+ , high Mg 2+ -containing extracellular
solution, indicating that the depolarization was primarily due to activation
of postsynaptic CCK receptors and not mediated through the release of other
neurotransmitters. 5. The selective CCK A antagonists, L364,718 and Cam-1481,
attenuated the CCK8S-induced depolarization, whereas the CCK B antagonist,
L365,260, had little or no effect on the depolarization. 6. Our findings
indicate that CCK8S, acting via CCK A type receptors, reduces a K + leak
current, resulting in a long-lasting membrane depolarization that can
presumably modify the firing mode of nRt neurons. Through this effect, CCK
actions in nRt may strongly influence thalamocortical function.
Received 31 January 1995; accepted in final form 17 April 1995.
APS Manuscript Number J66-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.