THE ACTIONS OF PROPOFOL ON INHIBITORY AMINO-ACID RECEPTORS OF BOVINE ADRENOMEDULLARY CHROMAFFIN CELLS AND RODENT CENTRAL NEURONS

1 The interaction of the intravenous general anaesthetic propofol (2,6-diisopropylphenol) with the GABA(A) receptor has been investigated in voltage-clamped bovine chromaffin cells and rat cortical neurones in cell culture. Additionally, the effects of propofol on the glycine and GABA(A) receptors of murine spinal neurones were determined. 2 Propofol (1.7-16.8-mu-M) reversibly and dose-dependently potentiated the amplitude of membrane currents elicited by GABA (100-mu-M) applied locally to bovine chromaffin cells. Intracellular application of propofol (16.8-mu-M) was ineffective. In rat cortical neurones and murine spinal neurones, extracellular application of 8.4-mu-M and 1.7-16.8-mu-M propofol respectively produced a potentiation of GABA-evoked currents qualitatively similar to that seen in the bovine chromaffin cell. 3 The potentiation by propofol (1.7-mu-M) was not associated with a change in the reversal potential of the GABA-evoked whole cell current. On outside-out membrane patches isolated from bovine chromaffin cells, propofol (1.7-mu-M) had little or no effect on the GABA single channel conductances, but greatly increased the probability of the GABA-gated channel being in the conducting state. 4 The potentiation of GABA-evoked whole cell currents by propofol (1.7-mu-M) was not influenced by the benzodiazepine antagonist flumazenil (0.3-mu-M). A concentration of propofol (1.7-mu-M) that substantially potentiated GABA currents had little effect on currents induced by the activation of the GABA(A) receptor by pentobarbitone (1 mM). 5 Bath application of propofol (8.4-252-mu-M), to bovine chromaffin cells voltage clamped at -60mV, induced an inward current associated with an increase in membrane current noise on all cells sensitive to GABA. Intracellular application of propofol (16.8-mu-M) was ineffective in this respect. Local application of propofol (600-mu-M) induced whole cell currents with a reversal potential dependent upon the Cl- gradient across the cell membrane. 6 On outside-out membrane patches formed from bovine chromaffin cells, propofol (30-mu-M) induced single channels with mean chord conductances of 29 and 12pS. The frequency of propofol channels was greatly reduced by coapplication of 1-mu-M bicuculline. Under identical ionic conditions, GABA (1-mu-M) activated single channels with mean chord conductances of 33, 16 and 10 pS. 7 Bath applied propofol (0.84-16.8-mu-M) dose-dependently potentiated strychnine-sensitive currents evoked by glycine (100-mu-M) in murine spinal neurones. 8 The relevance of the present results to the general anaesthetic action of propofol is discussed.