Contribution of a calcium-activated non-specific conductance to NMDA receptor-mediated synaptic potentials in granule cells of the frog olfactory bulb.

We studied granule cells (GCs) in the intact frog olfactory bulb (OB) by combining whole-cell recordings and functional two-photon Ca(2+) imaging in an in vitro nose-brain preparation. GCs are local interneurones that shape OB output via distributed dendrodendritic inhibition of OB projection neurones, the mitral-tufted cells (MTCs). In contrast to MTCs, GCs exhibited a Ca(2+)-activated non-specific cation conductance (I(CAN)) that could be evoked through strong synaptic stimulation or suprathreshold current injection. Photolysis of the caged Ca(2+) chelator o-nitrophenol-EGTA resulted in activation of an inward current with a reversal potential within the range -20 to +10 mV. I(CAN) in GCs was suppressed by the intracellular Ca(2+) chelator BAPTA (0.5-5.0 mM), but not by EGTA (up to 5 mM). The current persisted in whole-cell recordings for up to 1.5 h post-breakthrough, was observed during perforated-patch recordings and was independent of ionotropic glutamate and GABA(A) receptor activity. In current-clamp mode, GC responses to synaptic stimulation consisted of an initial AMPA-mediated conductance followed by a late-phase APV-sensitive plateau (100-500 ms). BAPTA-mediated suppression of I(CAN) resulted in a selective reduction of the late component of the evoked synaptic potential, consistent with a positive feedback relationship between NMDA receptor (NMDAR) current and I(CAN). I(CAN) requires Ca(2+) influx either through voltage-gated Ca(2+) channels or possibly NMDARs, both of which have a high threshold for activation in GCs, predicting a functional role for this current in the selective enhancement of strong synaptic inputs to GCs.