Short-term @entity1068 challenge results in the reduction of peptide hormone release from the @entity35 neurohypophysis. However, @entity35 that have been maintained on an @entity1068 -containing diet for 3 to 4 weeks exhibit tolerance to this effect. Mechanistic underpinnings of this tolerance were probed by examining four ion channel conductances critical for neurohormone release. The voltage-gated L-type @entity460 channel and the functionally linked @entity460 -activated BK channel represent a functional dyad. Although these channels show opposite drug responses in the naive terminal (i.e., the L-type @entity141 channel is inhibited whereas the BK channel is potentiated), the effect of long-term @entity167 exposure is to decrease sensitivity to the short-term administration of drug in both instances. In addition to the shift in sensitivity, current density increased for the L-type @entity141 current and decreased for the BK current, consistent with a compensatory change. Sensitivity to @entity167 was also altered for two other channel types studied. Inhibition of the voltage-gated transient @entity141 current was lessened after long-term treatment. I(A,) which is not sensitive to the drug at clinically relevant concentrations in terminals from the naive @entity35 , acquires sensitivity after long-term exposure, representing a potentially novel type of tolerance. However, neither the transient @entity141 current nor I(A) shows a change in current density, demonstrating the selectivity of this aspect of tolerance. Overall, these results demonstrate that channel plasticity can explain at least a portion of the behavioral tolerance resulting from changes in sensitivity of peptide hormone release. Furthermore, they suggest that an understanding of tolerance requires the examination of dynamically coupled channel populations.

Integrated channel plasticity contributes to XXXX tolerance in neurohypophysial terminals.

@entity167 :: ('CHEBI:16236', 'Chemical') :: ['alcohol'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['ethanol']
@entity167 :: (CHEBI:16236,Chemical) :: ['alcohol']
