The effects of propofol on hypothalamic paraventricular nucleus neurons in the rat

The mechanism of hypotension induced by anesthetics is not completely understood. Because no electrophysiologic examination of the effects of propofol on the central nervous system has shown its involvement in the control of sympathetic and cardiovascular functions, we investigated the actions of propofol on rat hypothalamic paraventricular nucleus (PVN) neurons using the whole-cell mode of the patch-clamp technique in rat hypothalamic PVN slice preparations. Propofol induced Cl(-) currents at concentrations of 10(-5) and 10(-4) M, which were sensitive to picrotoxin and, to a lesser extent, to strychnine. Propofol (10(-6) M) enhanced gamma-aminobutyric acid(A) (GABA(A); 10(-6) M)-induced current synergistically. Moreover, propofol (10(-5) and 10(-4) M) significantly increased the decay time of evoked-inhibitory postsynaptic currents, which suggests a postsynaptic modulation of GABA(A) receptors. In addition, propofol (10(-5), 10(-4), and 2 x 10(-4) M) reversibly inhibited voltage-gated Ca(2+) currents. Taken together, these results suggest that propofol enhancement of GABA(A)-receptor mediated currents and inhibition of voltage-gated Ca(2+) currents at the central level, which is involved in the control of cardiovascular and sympathetic functions may be, at least in part, involved in general anesthetic-induced cardiovascular and sympathetic depression.

We investigated the actions of propofol on the rat hypothalamic paraventricular nucleus neurons, which are involved in the control of cardiovascular and sympathetic functions. The results suggest that propofol enhancement of gamma-aminobutyric acid(A)-receptor mediated currents and inhibition of voltage-gated Ca(2+) currents at the central level may be, at least in part, involved in general anesthetic-induced cardiovascular and sympathetic depression.