K+ channels in PC12 cells are affected by propofol

Abstract

The effect on K+ currents (IK) of the general anaesthetic propofol (PR) (2,6-diisopropylphenol) was tested in undifferentiated clonal pheochromocytoma (PC 12) cells using the patch-clamp technique in whole-cell and single-channel configurations. PR decreased macroscopic IK amplitudes in a concentration-dependent way from 50 microM to 1 mM. The blocking effect was unchanged by repetitive depolarizing pulses and it was independent of the holding potential. Whereas activation of IK in control conditions was fitted by sigmoidal plus exponential time courses, only the sigmoidal time course gave an adequate fit with PR in the bath. The above effects were reversible. PR concentrations below 140 microM decreased single-channel activity for K+ channels with unitary conductance of 22 pS, in the voltage range between -40 and 60 mV from a holding potential of -50 mV. In contrast, the anaesthetic had nearly no effect on the opening probability of a channel with conductance of 10 pS. The unitary current amplitudes were unaffected in both channel types. These results suggest that PR action on IK may depend on the different blocking mechanisms of the K+ channels.

Inhibition by propofol (2,6 di‐isopropylphenol) of the N‐methyl‐D‐aspartate subtype of glutamate receptor in cultured hippocampal neurones

“…For example, the post-operative dreams, mood disturbances, and hallucinations observed following propofol anaesthesia, are more commonly associated with the dissociative anaesthetic ketamine (Young, 1988;Suresh, 1991;Oxorn et al, 1994). Propofol also blocks several non-ligand gated channels and exerts opposing actions on excitatory and inhibitory neurotransmitter receptors (Frenkel & Urban, 1991;Hales & Lambert, 1992;Magnelli et al, 1992;Veintemilla et al, 1992;Wachtel & Wegrzynowicz, 1992, Baum 1993Hara et al, 1993;Dilger et al, 1994;Olcese et al, 1994;Orser et al, 1994). Modulation of these receptors might also contribute to the clinical properties of propofol.…”

Major Role For Tonic GABAA Conductances in Anesthetic Suppression of Intrinsic Neuronal Excitability

“…This study is primarily focused on gaining a better understanding of the relative role (if any) of GABA tonic in producing depression of intrinsic neuronal excitability in neurons in intact acute brain slices, where the neuronal properties should be similar to in vivo. In the case of propofol, a widely used anesthetic, there are many sites of action that may affect intrinsic excitability, including effects on phasic (Trapani et al 2000) and tonic (Bai et al 2001) inhibition mediated by GABA A receptors (GABA A -Rs); sodium channels (Ratnakumari and Hemmings 1997;Rehberg and Duch 1999); potassium channels (Magnelli et al 1992); cation channels (I h ) (Higuchi et al 2003); calcium channels (Guertin and Hounsgaard 1999;Inoue et al 1999); glutamate channels (Orser et al 1995); and glutamate release (Ratnakumari and Hemmings 1997). Assuming that propofol suppresses intrinsic excitability, two critical questions emerge: is GABA tonic enhancement by anesthetics of sufficient magnitude to affect intrinsic excitability and given the existence of other proposed sites of propofol action that would affect intrinsic excitability, are effects on GABA tonic relatively dominant, relatively unimportant, or one contributor among many?…”

A discriminant block among K+ channel types by phenytoin in neuroblastoma cells

“…Three different types of delayed rectifier K + channels with conductance values of approximately 12, 15 and 18 pS and different kinetic behaviours were found in patches held at an HP of ‐50 mV. K + channels with similar conductances were observed in other preparations (Cook, 1988; Magnelli et al , 1992). The experiments reported in this paper show that phenytoin described the single‐channel activities of the three types of K + channels, whereas the unitary‐current amplitudes were unaffected.…”