Histamine potentiates acid sensing ion channels (ASICs) currents at the giant Calyx of Held synapse.

OSVALDO D. UCHITEL; CARLOTA GONZALEZ INCHAUSPE

Mar del Plata, Buenos Aires

Congreso; XXXII CONGRESO ANUAL de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2017

Sociedad Argentina de Investigación en Neurociencia (SAN)

ASICs play animportant function in physiologic processes and signal transduction associated withlocal and global extracellular pH variations during normal and pathologicalneuronal activity. We have identified homomeric ASIC1a-mediated currents duringsynaptic transmission at the calyx of Held synapse, suggesting an acidificationof the synaptic cleft due to the co-release of neurotransmitter and H+from synaptic vesicles. ASIC-1a current amplitudes are small relative to glutamatergicAMPA mediated excitatory postsynaptic currents. It is possible that someendogenous ligands may modulate ASICs and enhance their responses to physiologicallysignificant levels. Indeed, we have found that micromolar concentrations ofhistamine significantly potentiate ASIC-1a currents. This potentiation may bedue a shift of the activation dependence of ASIC-1a channels to less acidicconditions, increasing pH sensitivity. Histamine is involved in the immune andinflammatory response, and it also plays a role of a neurotransmitter in thecentral nervous system, regulating numerous physiological functions. The factthat histamine can target ASIC-1a channels is of great relevance since bothhistamine and ASIC receptors are implicated in many pathologies such as epilepsy, Alzheimer´sdisease, attention-deficit hyperactivity disorder, schizophrenia and multiplesclerosis.