BECAS
STAHL Agostina MÓnica
congresos y reuniones científicas
Título:
Kv7 channel openers and non-steroidal anti-inflammatory drugs decrease striatal cholinergic interneuron excitability
Autor/es:
PAZ, RODRIGO MANUEL; TUBERT, CECILIA; STAHL, AGOSTINA; MURER, M GUSTAVO; RELA, LORENA
Lugar:
Mar del Plata
Reunión:
Congreso; XXXII Congreso Anual SAN 2017; 2017
Institución organizadora:
Sociedad Argentina de Neurociencias
Resumen:
Striatal cholinergic interneurons (SCIN) have emerged as key modulators of the striatalcircuitry controlling voluntary movement. SCIN dysfunction has been involved in the genesisof movement disorders such as Parkinson´s disease (PD) and L-DOPA-induced dyskinesia(LID). Therefore, a better understanding of SCIN physiology may provide new potentialtherapeutic targets for PD and LID. SCIN are autonomous pacemakers and display spikefrequency accommodation in response to sustained current injection. Previous work foundthat blockade of Kv1 channels strongly increase SCIN excitability but the contribution of othervoltage-dependent potassium channels has been less studied. Here we aim to disclose therole of Kv7 currents in SCIN excitability. Blockers of Kv7 channels had no effect on SCINresponse to somatic current injection and spontaneous tonic firing but increased EPSPsummation induced by intrastriatal electrical stimulation. Retigabine, a Kv7 channel opener,markedly decreased SCIN excitability, which was restored by subsequent addition of XE991.Non-steroidal anti-inflamatory drugs (NSAIDs) may behave as Kv7 channel openers.Interestingly, diclofenac and meclofenamic acid reproduced the effect of retigabine in a dosedependentmanner but XE991 failed to reverse this effect, suggesting that NSAIDs decreaseSCIN excitability through a Kv7 independent mechanism. These results implicate Kv7 channelsand NSAIDs targets as key regulators of SCINs excitability.