Glutamate potentiates heterologously expressed homomeric acid-sensing ion channel 1a.

Acid-sensing ion channels (ASICs) participate in synaptic transmission due to the acidic content of synaptic vesicles, but their contribution to postsynaptic currents is small. This has stimulated attempts to find endogenous ASIC potentiators that could enhance ASIC-mediated currents to physiologically relevant values. Here we demonstrate that glutamate, which serves as a neurotransmitter, potentiates recombinant ASIC1a in the submillimolar concentration range.

Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents.

Early life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS).

Kainate receptors regulate development of glutamatergic synaptic circuitry in the rodent amygdala.

Perturbed information processing in the amygdala has been implicated in developmentally originating neuropsychiatric disorders. However, little is known on the mechanisms that guide formation and refinement of intrinsic connections between amygdaloid nuclei. We demonstrate that in rodents the glutamatergic connection from basolateral to central amygdala (BLA-CeA) develops rapidly during the first 10 postnatal days, before external inputs underlying amygdala-dependent behaviors emerge.

Hydrophobic Amines and Their Guanidine Analogues Modulate Activation and Desensitization of ASIC3.

Acid-sensing ion channel 3 (ASIC3) is an important member of the acid-sensing ion channels family, which is widely expressed in the peripheral nervous system and contributes to pain sensation. ASICs are targeted by various drugs and toxins. However, mechanisms and structural determinants of ligands' action on ASIC3 are not completely understood.

Multiple modes of action of hydrophobic amines and their guanidine analogues on ASIC1a.

Hydrophobic monoamines containing only a hydrophobic/aromatic moiety and protonated amino group are a recently described class of acid-sensing ion channel (ASIC) modulators. Intensive studies have revealed a number of active compounds including endogenous amines and pharmacological agents and shown that these compounds potentiate and inhibit ASICs depending on their specific structure and on subunit composition of the target channel. The action of monoamines also depends on the application protocol, membrane voltage, conditioning and activating pH, suggesting complex mechanism(s) of the ligand-receptor interaction.