Channel redistribution underlies alcohol tolerance of BK channels in terminals of rat neurohypophysis.

Tolerance is an important element of drug addiction and a model for understanding neuronal plasticity. The hypothalamo-neurohypophyseal system (HNS) has proven to be a useful preparation to study acute and chronic alcohol actions. Acute EtOH treatment of the isolated neurohypophysis (NH) inhibits AVP release from neuronal terminals, associated with reduction of voltage-gated Ca currents, and potentiation of BK currents. We previously reported that in rat, chronic EtOH diet results in the development of BK alcohol tolerance: 1/ the acute EtOH sensitivity of BK in the NH is decreased, and 2/BK current density is reduced. Here, we use an HNS explant to further explore the molecular mechanisms of tolerance. The HNS explant containing SON neurons with intact projections to the NH was isolated from an adult animal and optimized for cell viability. This model allowed us to precisely control concentration and temporal exposure to EtOH. EtOH tolerance of the BK channel is evident within 24 hr of drug exposure, and takes two forms, as previously observed in the intact animal: 1/ decreased sensitivity to EtOH, and 2/ reduced current density. We did not observe any change in kinetics, voltage dependency, conductance, or calcium sensitivity of individual BK channels. The decrease in BK current density was accompanied by a decrease in channel immuno-labeling in the periphery of tolerant terminals. Confocal, quantitative analysis of the BK signal in terminals revealed that chronic EtOH caused a reduction of BK channel clustering and decreased BK labeling in the remaining clusters. Thus, chronic EtOH exposure modulates BK channel sensitivity, density, and distribution pattern in NH terminals within the chronically-treated HNS explant, indicating that neuronal and non-neuronal influences from outside the HNS are not required for the development of tolerance.

Education
1997 Ph.D.Post Graduate Education Medical Center
1995 M.D. Warsaw University Medical School

Selected Publications

Pietrzykowski, A., Martin, G., Puig, S. and Treistman, (2004) S.N. Alcohol Tolerance in BK Channels of Neuronal Terminals is Intrinsic, and Includes Two Components: Decreased Channel Sensitivity to Ethanol and Decreased Channel Density. J Neurosci. 24(38):8322-32. Highlight of the week.

Martin, G., Puig, S.I., Pietrzykowski, A., Zadek, P.,Emery, P., and Treistman. S.N. (2004) Restricted cellular localization of a specific BK-channel subtype controls ethanol sensitivity in the nucleus accumbens, J. Neurosci. 24(29):6563-72.

Andrzej Pietrzykowski, Gilles Martin, Sylvie Puig and Steven Treistman. (2003) Channel Redistribution Underlies Alcohol Tolerance Of BK Channel In Terminals Of Rat Neurohypophysis. Neuroscience. Link to Poster.

Nauman A, Puzianowska-Kuznicka M, Pietrzykowski A, Grzesiuk W, Luczak J Nauman J. Iodothyronine-5’-deiodinase in the atrium and ventricle of the rat heart; 1998, Polish J. Endocrinology, 49, 261-270.

Nauman A, Nauman J, Pietrzykowski A, Lazecki D, Dutkiewicz S, Tanski Z, Witeska A, Kauczak M. The Low T3 Syndrome in patients with kidney cancer - effect of cancer differentiation. 1996, Polish J. Endocrinology, 47, 143-149.

Pietrzykowski A, Nauman A. Nuclear receptors for vitamin A derivatives. 1996, Polish J. Endocrinology, 3, 293-312.

Bednarczuk T, Pietrzykowski A, Slon M, Nauman A. Effects of pharmacological doses of iodine on thyroxine-5'-deiodinase activity in rat thyroid. 1993, Polish J. Endocrinology, 44, 4, 405-412.