BK channels in microglia

Large-conductance calcium-and voltage-dependent potassium(BK)channels are ubiquitously expressed in mammalian cells and participate in various physiological and pathological processes such as neurotransmission and cerebral ischemia.BK channels comprise up to four pore-formingαsubunits and zero to four accessory subunits.Although microglial BK currents were initially recorded 27 years ago,their roles have long been elusive.Studies have demonstrated that BK channels modulate the activation,phagocytosis,and probably migration of microglia and have associated microglial BK channels with many neurological diseases,including neuropathic pain and stroke.This review summarizes the available information regarding the biophysical,functional,and pathological aspects of microglial BK channels and discusses future directions of research into these channels.

Tuning the mechanosensitivity of a BK channel by changing the linker length

Some large-conductance Ca^2＋ and voltage-activated K^＋（BK） channels are activated by membrane stretch. However, the mechanism of mechano-gating of the BK channels is still not well understood. Previous studies have led to the proposal that the linker-gating ring complex functions as a passive spring, transducing the force generated by intracellular Ca^2＋ to the gate to open the channel. This raises the question as to whether membrane stretch is also transmitted to the gate of mechanosensitive （MS） BK channels via the linker-gating complex. To study this, we changed the linker length in the stretch-activated BK channel （SAKCaC）, and examined the effect of membrane stretch on the gating of the resultant mutant channels. Shortening the linker increased, whereas extending the linker reduced, the channel mechanosensitivity both in the presence and in the absence of intracellular Ca^2＋. However, the voltage and Ca^2＋ sensitivities were not significantly altered by membrane stretch. Furthermore, the SAKCaC became less sensitive to membrane stretch at relatively high intracellular Ca^2＋ concentrations or membrane depolarization. These observations suggest that once the channel is in the open-state conformation, tension on the spring is partially released and membrane stretch is less effective. Our results are consistent with the idea that membrane stretch is transferred to the gate via the linker-gating ring complex of the MS BK channels.

Mechanical force and cytoplasmic Ca^(2+) activate mechanosensitive BK channel in parallel

BK channels are widely expressed in both excitable and non-excitable cells and known to be involved in many physiological processes,such as vascular smooth tone regulation,neuronal firing and endocrine cell secretion[1].Recently, the BK channels have

Synthesis and BK channel-opening activity of novel N-acylhydrazone derivatives from dehydroabietic acid

A series of hydrazone and N-acylhydrazone derivatives of dehydroabietic acid were synthesized and evaluated for BK channel-opening activities in an assay system of CHO-K1 cells expressing hBKa channels.The assay results indicated that the activities of the investigated compounds were influenced by the physicochemical properties of the substituent at hydrazone moiety.

Nematodes feel a craving- Using Caenorhabditis elegans as a model to study alcohol addiction

Alcohol is the most frequently-used addictive drug. However, the mechanism by which its consumption leads to addiction remains largely elusive. Given the conservation of behavioral reactions to alcohol, Caenorhabitis elegans （C. elegans） has been effectively used as a model system to investigate the relevant molecular targets and pathways mediating these responses. In this article, we review the roles of BK channels （also called SLO-1）, the lipid microenvironment, receptors, the synaptic machinery, and neurotransmitters in both the acute and chronic effects of alcohol. We provide an overview of the genes and mechanisms involved in alcoholism- related behaviors in C. elegans.