Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons.

Abstract

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current IKir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of IKir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of IKir and hyperpolarization-activated cationic current Ih that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that IKir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with Ih and increases the robustness of low threshold-activated calcium current IT-mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current IKir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that IKir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current Ih; and increases the robustness of oscillations mediated by the low threshold-activated calcium current IT. Upregulation of IKir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).