Ca²⁺ permeability and kinetics of glutamate receptors in rat medial habenula neurones: implications for purinergic transmission in this nucleus

Abstract

We have previously investigated P2X receptor‐mediated synaptic currents in medial habenula neurones and shown that they can be calcium permeable. We now investigate the receptor properties of glutamate, the other, more abundant excitatory transmitter, to determine its receptor subtypes and their relative calcium permeability. This may have implications for the physiological role of the P2X receptors which mediate synaptic currents. Using fast application of ATP, L‐glutamate or kainate to nucleated patches, glutamate receptors were determined to be of the AMPA subtype but no functional P2X receptors were detected. The deactivation and desensitization rates of the AMPA channel were determined to have time constants of 1·77 ± 0·21 ms (n= 10) and 4·01 ± 0·85 ms (n= 9) at ‐60 mV, respectively. AMPA receptors recovered from desensitization with two exponential components with time constants of 21·08 ± 2·95 and 233·60 ± 51·1 ms (n= 3). None of the deactivation or desensitization properties of the GluR channels depended on membrane potential. The current‐voltage relationship under different ionic conditions revealed that the GluR channel was equally permeable to Cs+ and Na+ but relatively impermeable to Ca2+ (PCa/PCs= 0·13, n= 6). For both synaptic currents and somatic currents activated by fast application of L‐glutamate to nucleated patches, decay time constants were similar at ±60 mV in the presence of Mg2+ ions. Thus GluR channels appear to be of the AMPA subtype and not the NMDA subtype. Thus, under the conditions of this study, neurones of the medial habenula lack functional NMDA receptors and possess AMPA receptors that have low permeability to Ca2+. We conclude that the P2X receptor‐mediated synaptic currents are the only calcium‐permeable fast‐transmitter gated currents in these neurones which may be important for their physiological function.

Ketamine Reduces the Cell Death Following Inflammatory Pain in Newborn Rat Brain

“…3A). Minimal or no differences occurred in the thalamic nuclei or habenula, suggestive of low NMDA receptor activity (21). Post hoc analyses showed that cell death increased significantly in the F group, with no differences between the C, KF, and K groups.…”

The habenulo-interpeduncular pathway in nicotine aversion and withdrawal

“…In addition to nAChRs, MHb neurons express P2X receptors, which, upon ATP release from the TS, cause a substantial Ca 2+ influx into the neuron (Edwards et al, 1992; Edwards et al, 1997; Robertson et al, 1999; Rogers et al, 1997). Ca 2+ is an important intracellular messenger, modulating ion channels and altering synaptic function, and α4β2* and α3β4* nAChRs show a fairly high Ca 2+ -permeability (Ragozzino et al, 1998; Rathouz and Berg, 1994).…”

“…Ca 2+ is an important intracellular messenger, modulating ion channels and altering synaptic function, and α4β2* and α3β4* nAChRs show a fairly high Ca 2+ -permeability (Ragozzino et al, 1998; Rathouz and Berg, 1994). Together, P2X and nAChRs, likely make up for the lack of Ca 2+ current mediated by NMDARs, which are not expressed in the MHb (Robertson et al, 1999; Rogers and Dani, 1995). Functionally, ATP has been shown to both depolarize and increase spontaneous AP activity in hypocretin/orexin neurons (Wollmann et al, 2005).…”

Imaging single-channel calcium microdomains

“…Nevertheless, numerous types of ion channels show appreciable permeability to Ca 2+ (summarized in Table 1), so imaging of SCCaFTs has widespread potential applicability. The various families of voltage-gated Ca 2+ channels are the most obvious mechanisms for regulating plasma membrane Ca 2+ flux, but growing evidence emphasizes also the importance of numerous ligand-gated channels [39][40][41][42][43][44][45], among which attention has focused on nicotinic acetylcholine receptors (nAChRs) and ionotropic glutamate receptors (GluR) because of their involvement in synaptic transmission.…”