Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol.

Tolerance represents a critical component of addiction. The large-conductance calcium- and voltage-activated potassium channel (BK) is a well-established alcohol target, and an important element in behavioral and molecular alcohol tolerance. We tested whether microRNA, a newly discovered class of gene expression regulators, plays a role in the development of tolerance.

Alcohol tolerance in large-conductance, calcium-activated potassium channels of CNS terminals is intrinsic and includes two components: decreased ethanol potentiation and decreased channel density.

Tolerance is an important element of drug addiction and provides a model for understanding neuronal plasticity. The hypothalamic-neurohypophysial system (HNS) is an established preparation in which to study the actions of alcohol. Acute application of alcohol to the rat neurohypophysis potentiates large-conductance calcium-sensitive potassium channels (BK), contributing to inhibition of hormone secretion.