Intracellular BK_Ca (iBK_Ca) channels

Abstract

The large conductance calcium-and voltage-activated potassium channel (BK Ca ) is widely expressed at the plasma membrane. This channel is involved in a variety of fundamental cellular functions including excitability, smooth muscle contractility, and Ca 2+ homeostasis, as well as in pathological situations like proinflammatory responses in rheumatoid arthritis, and cancer cell proliferation. Immunochemical, biochemical and pharmacological studies from over a decade have intermittently shown the presence of BK Ca in intracellular organelles. To date, intracellular BK Ca (iBK Ca ) has been localized in the mitochondria, endoplasmic reticulum, nucleus and Golgi apparatus but its functional role remains largely unknown except for the mitochondrial BK Ca whose opening is thought to play a role in protecting the heart from ischaemic injury. In the nucleus, pharmacology suggests a role in regulating nuclear Ca 2+ , membrane potential and eNOS expression. Establishing the molecular correlates of iBK Ca , the mechanisms defining iBK Ca organelle-specific targeting, and their modulation are challenging questions. This review summarizes iBK Ca channels, their possible functions, and efforts to identify their molecular correlates.

The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease

“…Mechanistically, it seems that 11,12-EET induces the physical association of the BKa and BKb1 subunits on the mitochondrial membrane (Loot et al, 2012). Whether this is a phenomenon exclusive to pulmonary VSMCs remains to be clarified but is of potential interest given that mitochondrial BK channels in the heart are thought to play a role in protection from ischemic injury (for review, see Singh et al, 2012) and both EETs and sEH inhibition protect mitochondrial function after stress (Katragadda et al, 2009;Batchu et al, 2012b).…”

Ca²⁺-Activated K⁺ Channels as Therapeutic Targets for Myocardial and Vascular Protection

“…3,7,8 Mitochondrial BKCa channel expression has been controversial, presumably because of the low levels of expression and less than optimal available antibodies. BKCa-like currents in mitochondria were first described by Xu et al, who also showed significant cardioprotection using the BKCa activator NS1619 in guinea pig hearts.…”

Upregulation of the large conductance voltage- and Ca2+-activated K+ channels by Janus kinase 2

“…The observed effect of JAK2 and V617F JAK2 on the large conductance voltage-and Ca 2ϩ -activated K ϩ channels may be relevant for proliferation, migration, and metastasis of tumor cells (15,50,52,54,63,67). However, in some cells other K ϩ channels may functionally replace the BK channels and thus inhibition of BK channels does not necessarily interfere with those functions.…”