Mitral Cells of the Olfactory Bulb Perform Metabolic Sensing and Are Disrupted by Obesity at the Level of the Kv1.3 Ion Channel
Figure 7
Insulin inhibits voltage-activated currents in adult mitral cells that are carried predominantly by Kv1.3 channels.
(A) Representative current-clamp recording in a mitral cell prior (Control) and following a two minute bath application of the sea anemonie-derived channel peptide (ShK186). Evoked activity was elicited using a 1 s long current injection of 25 pA while recording near the natural resting potential of -65 mV. (B) Representative family of voltage-activated currents elicited in a mitral cell that was stepped in 10 mV depolarizing increments of 400 ms duration to a Vc = +40 mV from a holding potential of -80 mV. Tetrodotoxin was added to control ACSF (Control, TTX) to eliminate unwanted sodium channel activity that would contribute to unwanted spiking. The subtraction trace represents the Kv1.3 contribution to the total mitral cell outward current. (C) (left) Same voltage paradigm as in panel B. The cell was first recorded in control ACSF (Control), followed by a 20 minute bath application of insulin (Insulin). (Right) Bar plot of the mean (± s.e.m.) peak transient or sustained outward current prior (black bar) and following insulin (stripped bar) stimulation. * = Significantly different by paired t-test, α≤0.05. (D) Same cell as in panel C, where TTX was then added to isolate outward currents and finally ShK186 was applied to uncover the Kv1.3 contribution that was modulated by insulin (Insulin, TTX, ShK186). The unidentified residual current is mediated by channels that are both insulin and ShK186 resistant. The subtraction trace represents the remaining Kv1.3 and Na channel contributions that were not modulated by insulin.