Lack of Regulation by Intracellular Ca2+ of the Hyper Polarization‐Activated Cation Current in Rat Thalamic Neurones

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Abstract
The regulation of the hyperpolarization‐activated cation current, Ih, in thalamocortical neurones by intracellular calcium ions has been implemented in a number of mathematical models on the waxing and waning behaviour of synchronized rhythmic activity in thalamocortical circuits. In the present study, the Ca2+ dependence of Ih in thalamocortical neurones was experimentally investigated by combining Ca2+ imaging and patch‐clamp techniques in the ventrobasal thalamic complex (VB) in vitro. Properties of Ih were analysed before and during rhythmic stimulation of Ca2+ entry by trains of depolarizing voltage pulses. Despite a significant increase in intracellular Ca2+ concentration ([Ca2+]i) from resting levels of 74 ± 23 nM to 251 ± 78 nM upon rhythmic stimulation, significant differences in the voltage dependence of Ih activation did not occur (half‐maximal activation at −86.4 ± l.3 mV vs.−85.2 ± 2.9 mV; slope of the activation curve, 11.2 ± 2.4 mV vs. 12.5 ± 2.5 mV). Recording of Ih with predefined values of [Ca2+]i (13.2 nM or 10.01 μm in the patch pipette) revealed no significant differences in the activation curve or the fully activated I–V relationship of Ih. In comparison, stimulation of the intracellular cyclic adenosine monophosphate (cAMP) pathway induced a significantly positive shift in Ih voltage dependence of +5.1 ± l.9 mV, with no alteration in the fully activated I–V relationship. These data argue against a direct regulation of Ih by intracellular Ca2+, and particularly do not support a primary role of Ca2+‐dependent modulation of the Ih channels in the waxing and waning of sleep spindle oscillations in thalamocortical neurones.