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

摘要

class="enumerated" style="list-style-type:decimal">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.