A large-conductance calcium-regulated K+ channel in human dermal fibroblast mitochondria

Abstract

Potassium channels have been found in the inner mitochondrial membrane of various cells. These channels regulate the mitochondrial membrane potential, respiration and production of reactive oxygen species. In the present study, we identified the activity of a mitochondrial large-conductance Ca²⁺-regulated potassium channel (mitoBK_Ca channel) in mitoplasts isolated from a primary human dermal fibroblast cell line. A potassium selective current was recorded with a mean conductance of 280 ± 2 pS in a symmetrical 150 mM KCl solution. The mitoBK_Ca channel was activated by the Ca²⁺ and by potassium channel opener NS1619. The channel activity was irreversibly inhibited by paxilline, a selective inhibitor of the BK_Ca channels. In isolated fibroblast mitochondria NS1619 depolarized the mitochondrial membrane potential, stimulated nonphosphorylating respiration and decreased superoxide formation. Additionally, the α- and β-subunits (predominantly the β3-form) of the BK_Ca channels were identified in fibroblast mitochondria. Our findings indicate, for the first time, the presence of a large-conductance Ca²⁺-regulated potassium channel in the inner mitochondrial membrane of human dermal fibroblasts.