|Title||Effects of propofol on sodium channel-dependent sodium influx and glutamate release in rat cerebrocortical synaptosomes.|
|Publication Type||Journal Article|
|Year of Publication||1997|
|Authors||Ratnakumari L, Hemmings HC|
|Date Published||1997 Feb|
|Keywords||4-Aminopyridine, Anesthetics, Intravenous, Animals, Calcium Channels, Cerebral Cortex, Glutamic Acid, Male, Potassium Chloride, Propofol, Rats, Rats, Sprague-Dawley, Sodium, Sodium Channel Blockers, Sodium Channels, Sodium-Potassium-Exchanging ATPase, Synaptosomes, Veratridine|
BACKGROUND: Previous electrophysiologic studies have implicated voltage-dependent Na+ channels as a molecular site of action for propofol. This study considered the effects of propofol on Na+ channel-mediated Na+ influx and neurotransmitter release in rat brain synaptosomes (isolated presynaptic nerve terminals).
METHODS: Purified cerebrocortical synaptosomes from adult rats were used to determine the effects of propofol on Na+ influx through voltage-dependent Na+ channels (measured using 22Na+) and intracellular [Na+] (measured by ion-specific spectrofluorimetry). For comparison, the effects of propofol on synaptosomal glutamate release evoked by 4-aminopyridine (Na+ channel dependent), veratridine (Na+ channel dependent), KCi (Na+ channel independent) were studied using enzyme-coupled fluorimetry.
RESULTS: Propofol inhibited veratridine-evoked 22Na+ influx (inhibitory concentration of 50% [IC50] = 46 microM; 8.9 microM free) and changes in intracellular [Na+] (IC50 = 13 microM; 6.3 microM free) in synaptosomes in a dose-dependent manner. Propofol also inhibited 4-aminopyridine-evoked (IC50 = 39 microM; 19 microM free) and veratridine (20 microM)-evoked (IC50 = 30 microM; 14 microM free), but not KCi-evoked (up to 100 microM) glutamate release from synaptosomes.
CONCLUSIONS: Inhibition of Na+ channel-mediated Na+ influx, increased in intracellular [Na+], and glutamate release occurred in synaptosomes at concentrations of propofol achieved clinically. These results support a role for neuronal voltage-dependent Na+ channels as a molecular target for presynaptic general anesthetic effects.
|Grant List||GM 52441 / GM / NIGMS NIH HHS / United States|