| 16093340 |
Chen X, Shu S, Bayliss DA: Suppression of ih contributes to propofol-induced inhibition of mouse cortical pyramidal neurons. J Neurophysiol. 2005 Dec;94(6):3872-83. Epub 2005 Aug 10.
The contributions of the hyperpolarization-activated current, I (h), to generation of rhythmic activities are well described for various central neurons, particularly in thalamocortical circuits. In the present study, we investigated effects of a general anesthetic, propofol, on native I (h) in neurons of thalamus and cortex and on the corresponding cloned HCN channel subunits. Whole cell voltage-clamp recordings from mouse brain slices identified neuronal I (h) currents with fast activation kinetics in neocortical pyramidal neurons and with slower kinetics in thalamocortical relay cells. Propofol inhibited the fast-activating I (h) in cortical neurons at a clinically relevant concentration (5 microM); inhibition of I (h) involved a hyperpolarizing shift in half-activation voltage (DeltaV1/2 approximately -9 mV) and a decrease in maximal available current (approximately 36% inhibition, measured at -120 mV). With the slower form of I (h) expressed in thalamocortical neurons, propofol had no effect on current activation or amplitude. In heterologous expression systems, 5 muM propofol caused a large shift in V1/2 and decrease in current amplitude in homomeric HCN1 and linked heteromeric HCN1-HCN2 channels, both of which activate with fast kinetics but did not affect V1/2 or current amplitude of slowly activating homomeric HCN2 channels. With GABA (A) and glycine receptor channels blocked, propofol caused membrane hyperpolarization and suppressed action potential discharge in cortical neurons; these effects were occluded by the I (h) blocker, ZD-7288. In summary, these data indicate that propofol selectively inhibits HCN channels containing HCN1 subunits, such as those that mediate I (h) in cortical pyramidal neurons-and they suggest that anesthetic actions of propofol may involve inhibition of cortical neurons and perhaps other HCN1-expressing cells. |
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