Lack of regulation by intracellular Ca2+ of the hyperpolarization-activated cation current in rat thalamic neurones

1. The regulation of the hyperpolarization-activated cat ion current, I-h, 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 I-h in thalamocortical neurones was experimentally investigated by combining Ca2+ imaging and patch-clamp techniques in the ventrobasal thalamic complex (VB) in vitro. 2. Properties of I-h 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 I-h activation did not occur (half-maximal activation at -86.4 +/- 1.3 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 I-h with predefined values of [Ca2+](i) (13.2 nM or 10.01 mu M in the patch pipette) revealed no significant differences in the activation curve or the fully activated I-V relationship of I-h. 3. In comparison, stimulation of the intracellular cyclic adenosine monophosphate (cAMP) pathway induced a significantly positive shift in I-h voltage dependence of +5.1 +/- 1.9 mV, with no alteration in the fully activated I-V relationship. 4. These data argue against a direct regulation of I-h by intracellular Ca2+, and particularly do not support a primary role of Ca2+-dependent modulation of the I-h channels in the waxing and waning of sleep spindle oscillations in thalamocortical neurones.