Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a K+ conductance

Abstract

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 octapeptide (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 0.6-3.8 nS, which amounted to 5-54% 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 the potassium equilibrium potential. Modifications of extracellular K+ concentration 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 extracellularly, blocked the response to CCK8S. 4. The CCK8S-induced depolarization persisted after suppression of synaptic transmission by either tetrodotoxin or a low-Ca2+, high-Mg2+ 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 CCKA antagonists L364,718 and Cam-1481 attenuated the CCK8S-induced depolarization, whereas the CCKB antagonist L365,260 had little or no effect on the depolarization. 6. Our findings indicate that CCK8S, acting via CCKA-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.

Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others

“…In contrast, PV-expressing basket cells could be the source of IPSPs that are sensitive to agatoxin, but insensitive to direct stimulation by CCh, or inhibition by endocannabinoids. Our data suggest that CCK may directly excite PV interneurons (probably via the inhibition of an resting K + conductance as suggested by Cox et al, 1995 andMiller et al, 1997), while indirectly inhibiting the CCK-interneurons via GABA (since the inhibition was blocked by a GABA B antagonist). An unresolved but important issue is exactly where the CCK 2 receptors are located.…”

Cholecystokinin-8S-Induced Intracellular Calcium Signaling in Acutely Isolated Periaqueductal Gray Neurons of the Rat

“…For example, application of CCK has been known to produce a membrane depolarization or an inward current in the hippocampus, nucleus accumbens, and thalamus. 32,35,36) In most studies, including our previous one, 25) CCK-induced inward current was accompanied with a decreased membrane conductance and intersected near the K ϩ ion reversal potential. All together, these results suggest that CCK produced excitatory effects through an inhibition of K ϩ channels.…”

Vasoactive Intestinal Peptide Selectively Depolarizes Thalamic Relay Neurons and Attenuates Intrathalamic Rhythmic Activity

“…Based on the rate of VIP injection and the rate of chamber perfusion, the final bath concentration of VIP was estimated to one-eighth of the concentration introduced in the flow line (Cox et al 1995). Control injections of physiological saline produced neither changes in intrathalamic activity during extracellular recording or changes in membrane potential or input resistance during current-clamp recordings, suggesting that the temporary increase in flow rate during the bolus injections had no effect on the recordings.…”

“…The functional significance of these modulators within thalamic nuclei has remained somewhat elusive. However, recent studies have scratched the surface regarding peptide actions in the thalamus, demonstrating that these compounds may alter passive membrane characteristics of thalamic neurons such as resting membrane potential, input resistance, and membrane conductance, and in some cases, such actions can modulate intrathalamic rhythmic activities (Cox et al 1995(Cox et al , 1997Leresche et al 2000;Sun et al 2001).…”