Insulin Facilitates Repetitive Spike Firing in Rat Insular Cortex via Phosphoinositide 3-kinase but Not Mitogen Activated Protein Kinase Cascade

Neuroscience. 2010 Nov 10;170(4):1199-208. doi: 10.1016/j.neuroscience.2010.07.061. Epub 2010 Aug 5.

Abstract

The insular cortex (IC) processes gustatory and visceral information, which functionally correlate to feeding behavior. Insulin, a well-known hormone controlling glucose metabolism, is released by elevation of blood glucose concentration following feeding behavior. The IC expresses dense insulin receptors and receives projection from the hypothalamus, which monitors changes in glucose concentration. Therefore, it is likely that insulin modulates neural properties in the IC. However, little is known about the effects of insulin on electrophysiological properties of the neocortex including the IC. To explore the effects of insulin on subthreshold responses and action potential properties in the IC, intracellular recording with sharp glass electrodes was performed from IC pyramidal cells using slice preparations. Although application of insulin (100 nM) had little effect on the resting membrane potential, input resistance and rheobase, insulin significantly increased the frequency of repetitive spike firing in response to a long depolarizing current pulse injection: the slope of the frequency-current curve was increased from 23.7±2.3 Hz/nA to 29.5±3.4 Hz/nA. Insulin slightly decreased the action potential threshold without affecting the amplitude of medium-duration and slow afterhyperpolarization (sAHP) s. The insulin-induced facilitation of repetitive spike firing was dose-dependent and blocked by pre-application of 200 nM lavendustin A, a tyrosine kinase inhibitor. Moreover, when combined with 200 nM wortmannin, a phosphoinositide 3-kinase (PI3-K) inhibitor, or 500 nM deguelin, an inhibitor of protein kinase B (PKB/Akt) downstream of PI3-K, insulin failed to increase the frequency of repetitive spike firing. In contrast, co-application of insulin and (10 μM) PD 98059, an inhibitor of mitogen activated protein kinase (MAPK), exerted facilitation of repetitive spike firing. These results suggest that acute insulin-induced facilitation of firing frequency is at least partially induced by hyperpolarizing effects on the action potential threshold, and that this facilitation is induced by activation of PI3-K but not MAPK cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Female
  • In Vitro Techniques
  • Insulin / pharmacology
  • Insulin / physiology*
  • MAP Kinase Signaling System / physiology*
  • Male
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Phosphatidylinositol 3-Kinase / physiology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Rats
  • Rats, Wistar

Substances

  • Insulin
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphatidylinositol 3-Kinase
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases