Cross‐talking between 5‐HT 3 and GABA A receptors in cultured myenteric neurons

We recorded whole‐cell ion currents induced by γ‐aminobutyric acid (I GABA ) and serotonin (I 5‐HT ) to investigate and characterize putative interactions between GABA A and 5‐HT 3 receptors in myenteric neurons from the guinea pig small intestine. I GABA and I 5‐HT were inhibited by bicuculline and ondansetron, respectively. Currents induced by the simultaneous application of both, GABA and 5‐HT (I GABA+5‐HT ) were significantly lower than the sum of I GABA and I 5‐HT , indicating the existence of a current occlusion. Such an occlusion was observed when GABA A and 5‐HT 3 receptors are virtually saturated. Kinetics, and pharmacological properties of I GABA+5‐HT indicate that they are mediated by activation of both, GABA A and 5‐HT 3 channels. GABA did not alter I 5‐HT in neurons without GABA A channels, in the presence of bicuculline (a GABA A receptor antagonist) or at the reversal potential for I GABA . Similarly, 5‐HT did not modify I GABA in neurons in which 5‐HT 3 channels were absent, after inhibiting 5‐HT 3 channels with ondansetron (a 5‐HT 3 receptor antagonist) or at the reversal potential for I 5‐HT . Current occlusion was observed as soon as GABA A and 5‐HT 3 channels were being activated, in the absence of Ca 2+ , at low temperature (11°C), and after adding staurosporine (a protein kinase inhibitor) to the pipette solution. Our proposal is that GABA A and 5‐HT 3 channels are organized in clusters and within these, both channels can cross‐inhibit each other, likely by allosteric interactions between these proteins. Synapse 61:732–740, 2007. © 2007 Wiley‐Liss, Inc.