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.