This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Shirasaka, T. Articles by Takasaki, M. Search for Related Content PubMed PubMed Citation Articles by Shirasaka, T. Articles by Takasaki, M. Related Collections Mechanisms Neuroanesthesia Pharmacology

---

ANESTHETIC PHARMACOLOGY

The Effects of Propofol on Hypothalamic Paraventricular Nucleus Neurons in the Rat

Tetsuro Shirasaka^*, Yasuhiro Yoshimura^*, De-Lai Qiu, and Mayumi Takasaki^*

Departments of *Anesthesiology and Physiology, Miyazaki Medical College, Kiyotake, Japan

Address correspondence and reprint requests to Tetsuro Shirasaka, Department of Anesthesiology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889–1692, Japan. Address e-mail to shirasak{at}med.miyazaki-u.ac.jp

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 -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 Ca²⁺ currents. Taken together, these results suggest that propofol enhancement of GABA_A-receptor mediated currents and inhibition of voltage-gated Ca²⁺ 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.

IMPLICATIONS: 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 Ca²⁺ currents at the central level may be, at least in part, involved in general anesthetic-induced cardiovascular and sympathetic depression.

This article has been cited by other articles:

				K.-Y. Li, C. Xiao, M. Xiong, E. Delphin, and J.-H. Ye Nanomolar Propofol Stimulates Glutamate Transmission to Dopamine Neurons: A Possible Mechanism of Abuse Potential? J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 165 - 174. [Abstract] [Full Text] [PDF]

				S.-W. Ying and P. A. Goldstein Propofol-Block of SK Channels in Reticular Thalamic Neurons Enhances GABAergic Inhibition in Relay Neurons J Neurophysiol, April 1, 2005; 93(4): 1935 - 1948. [Abstract] [Full Text] [PDF]