The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones
TG Hales, JJ Lambert - British journal of pharmacology, 1991 - Wiley Online Library
TG Hales, JJ Lambert
British journal of pharmacology, 1991•Wiley Online Library1 The interaction of the intravenous general anaesthetic propofol (2, 6‐diisopropylphenol)
with the GABAA 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 GABAA receptors of murine spinal neurones were determined. 2 Propofol (1.7–16.8 μm)
reversibly and dose‐dependently potentiated the amplitude of membrane currents elicited
by GABA (100 μm) applied locally to bovine chromaffin cells. Intracellular application of …
with the GABAA 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 GABAA receptors of murine spinal neurones were determined. 2 Propofol (1.7–16.8 μm)
reversibly and dose‐dependently potentiated the amplitude of membrane currents elicited
by GABA (100 μm) applied locally to bovine chromaffin cells. Intracellular application of …
- 1The interaction of the intravenous general anaesthetic propofol (2,6‐diisopropylphenol) with the GABAA 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 GABAA receptors of murine spinal neurones were determined.
- 2Propofol (1.7–16.8 μm) reversibly and dose‐dependently potentiated the amplitude of membrane currents elicited by GABA (100 μm) applied locally to bovine chromaffin cells. Intracellular application of propofol (16.8 μm) was ineffective. In rat cortical neurones and murine spinal neurones, extracellular application of 8.4 μm and 1.7–16.8 μm propofol respectively produced a potentiation of GABA‐evoked currents qualitatively similar to that seen in the bovine chromaffin cell.
- 3The potentiation by propofol (1.7 μm) 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 μm) 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.
- 4The potentiation of GABA‐evoked whole cell currents by propofol (1.7 μm) was not influenced by the benzodiazepine antagonist flumazenil (0.3 μm). A concentration of propofol (1.7 μm) that substantially potentiated GABA currents had little effect on currents induced by the activation of the GABAA receptor by pentobarbitone (1 mm).
- 5Bath application of propofol (8.4–252 μm), to bovine chromaffin cells voltage clamped at −60 mV, induced an inward current associated with an increase in membrane current noise on all cells sensitive to GABA. Intracellular application of propofol (16.8 μm) was ineffective in this respect. Local application of propofol (600 μm) induced whole cell currents with a reversal potential dependent upon the Cl− gradient across the cell membrane.
- 6On outside‐out membrane patches formed from bovine chromaffin cells, propofol (30 μm) induced single channels with mean chord conductances of 29 and 12 pS. The frequency of propofol channels was greatly reduced by coapplication of 1 μm bicuculline. Under identical ionic conditions, GABA (1 μm) activated single channels with mean chord conductances of 33, 16 and 10 pS.
- 7Bath applied propofol (0.84–16.8 μm) dose‐dependently potentiated strychnine‐sensitive currents evoked by glycine (100 μm) in murine spinal neurones.
- 8The relevance of the present results to the general anaesthetic action of propofol is discussed.
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