Localization of CCK receptors in thalamic reticular neurons: a modeling study.
In an earlier experimental study, intracellular recording suggested that cholecystokinin (CCK) suppresses a K+ conductance in thalamic reticular (RE) neurons, yet the reversal potential of the CCK response, revealed using voltage clamp, was hyperpolarized significantly relative to the K+ equilibrium potential. Here, biophysical models of RE neurons were developed and used to test whether suppression of the K+ conductance, gK, can account for the CCK response observed in vitro and also to determine the likely site of CCK receptors on RE neurons. Suppression of gK in model RE neurons can reproduce the relatively hyperpolarized reversal potential of CCK responses found using voltage clamp if the voltage clamp becomes less effective at hyperpolarized potentials. Three factors would reduce voltage-clamp effectiveness in this model: the nonnegligible series resistance of the voltage-clamp electrode, a hyperpolarization-activated mixed cation current (Ih) in RE neurons, and the dendritic location of CCK-sensitive K+ channels. Although suppression of gK in the dendritic compartments of model RE neurons simulates both the magnitude and reversal potential of the CCK response, suppression of gK in just the somatic compartment of model RE neurons fails to do so. Thus the model predicts that CCK should effectively suppress K+ conductance RE neuron dendrites and thereby regulate burst firing in RE neurons. This may explain the potent effects of CCK on intrathalamic oscillations in vitro.
Sohal
V S
VS
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305-5122, USA.
Cox
C L
CL
Huguenard
J R
JR
D000818:Animals; D002766:Cholecystokinin / Q000819:agonists / Q000494:pharmacology; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology; D017136:Ion Transport; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000737:chemistry*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000032:analysis*; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013787:Thalamic Nuclei / Q000737:chemistry*
C090019:8-sulfocholecystokinin octapeptide; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D012844:Sincalide; D011188:Potassium