The large conductance calcium-activated potassium (BK) channels play prominent roles in cellular activity ranging from modulating neuronal repolarization to mediating vasculature contractions in the periphery. The BK channels are sensitive to changes in membrane potential and/or calcium ion levels. Association with any of the four β-subunits modulates kinetics, voltage dependence, and calcium ion sensitivity. In this issue, Wynne et al., describe a study of the rat hypothalamic-neurohypophysial system (HNS). The HNS system is ideal for identification of channel distribution because the dendrite, cell body, and nerve terminal are easily distinguished. The dendritic and somatic channels have fast gating kinetics, whereas the nerve termini exhibit slow BK channel gating. Only the latter channels are sensitive to iberiotoxin but much less sensitive to calcium ions. Although the nerve terminal channels are potentiated by ethanol, the dendritic and somatic channels are insensitive. Immunohistochemical analyses showed that there are distinct clusters of the β-1 BK subunits in the somatic and dendritic regions, with little or no β-4 subunit expression. In contrast, the nerve endings express only the β-4 BK subunit. These results demonstrate that regional differences in β subunits to the BK channels modulate excitability and response to alcohol. Given that these regions also excrete neurohormonal peptides, such as oxytocin and vasopressin, these results provide insights into how regional differences in subunit composition can affect calcium ion thresholds, leading to variations on neurohormone secretion functional responses.
See article at J Pharmacol Exp Ther 2009, 329:978-986.
- The American Society for Pharmacology and Experimental Therapeutics