Live presentation

Asynchronous discussion

P#210

Altered HCN channel function in thalamic ventrobasal neurons of leptin-deficient mice

Paula Patricia Perissinotti

  • CABA,
  • Argentina
  • Paula Perissinotti ¹
  • , Lucila Kargieman ¹
  • , Agustin Rocha ¹
  • , Tomas Grosso ¹
  • , Francisco Urbano ¹
  • 1 IFIBYNE-UBA-CONICET

The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel is a voltage-gated ion channel that carry the H-current (IH). The expression of HCN1-4 isoforms is abundant in the thalamus. This channel is activated at sub-threshold potentials and works as an intrinsic and slow voltage-clamp that tends to stabilize the resting membrane potential, regulating the neuronal excitability and the synaptic integration. Leptin is a pleiotropic hormone that regulates numerous CNS functions. The dense distribution of leptin receptor mRNA in the thalamus suggests that leptin could act as a neuromodulator of thalamocortical activity. Here, we studied the electrophysiological expression of IH in ventrobasal (VB) neurons in brain slices from wildtype (WT) or the leptin-deficient mouse (ob/ob). IH density was increased by 22% in WT females compared to WT males. However, IH density was altered regardless of the gender in the ob/ob mice. Similarly, IH density decreased by 22% in ob/ob males (WT, n=23; ob/ob, n=22) and 16% in ob/ob females (WT, n=14; ob/ob, n=11). The time constant of deactivation was slower in the ob/ob compared to the WT for either males or females. In order to study whether IH alterations could be reversed, leptin was injected in vivo through a cannula implanted in the VB nucleus of ob/ob mice. We found that 24 hours after injecting leptin, IH density reached values as observed in WT, confirming that alterations of HCN channel function could be reversed by leptin.

Sorry, but you don’t have permission to view this content.