Altered pacemaker currents in thalamic ventrobasal neurons of leptin-deficient mice

PERISSINOTTI, PAULA P.; CELESTE RIVERO ECHETO; GARCIA-RILL, EDGAR; BISAGNO, VERÓNICA; URBANO, FRANCISCO J.

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) and KV7 (M) channels are voltage-gated ion channels that carry h and M currents, respectively (Ih, IM). The expression of HCN1-4, Kv7.2 and Kv7.3 isoforms is abundant in the thalamus. Both channels are activated at sub-threshold potentials and have biophysical properties that mirror each other. Because of their opposite voltage dependences and directions, they both function similarly as intrinsic, slow ?voltage clamps?, tending to stabilize the resting membrane potential (RMP) by opposing depolarizing or hyperpolarizing inputs. Subtle modifications of RMP impact on T-type calcium channels, and this has profound consequences for action potential (AP) generation. Here, we studied the electrophysiological expression of h, M and T-type currents in ventrobasal (VB) neurons in brain slices from wildtype (WT) or the leptin-deficient mouse (ob/ob). Ih density and its kinetic properties were altered in ob/ob mice. Ih density decreased by 30% (WT, n=19; ob/ob, n=21) and both, time constants of activation and deactivation were increased (WT, n=14; ob/ob, n=20). The IM blocker XE991 sped up Ih activation and deactivation kinetics but only in ob/ob (n=7) and not in WT (n=9) mice, suggesting an IM overexpression in the ob/ob. Depolarization conveyed by a decreased Ih activation in ob/ob neurons diminished the de-inactivation of T-type channels, thereby altering the generation of an LTS, which in turn triggers a burst of APs.