Coassembly of big conductance Ca2+-activated K+ channels and L-type voltage-gated Ca2+ channels in rat brain

Abstract

Based on electrophysiological studies, Ca2+-activated K + channels and voltage-gated Ca2+ channels appear to be located in close proximity in neurons. Such colocalization would ensure selective and rapid activation of K+ channels by local increases in the cytosolic calcium concentration. The nature of the apparent coupling is not known. In the present study we report a direct coassembly of big conductance Ca2+-activated K+ channels (BK) and L-type voltage-gated Ca2+ channels in rat brain. Saturation immunoprecipitation studies were performed on membranes labeled for BK channels and precipitated with antibodies against α1C and α1D L-type Ca 2+ channels. To confirm the specificity of the interaction, precipitation experiments were carried out also in reverse order. Also, additive precipitation was performed because α1C and α1D L-type Ca2+ channels always refer to separate ion channel complexes. Finally, immunochemical studies showed a distinct but overlapping expression pattern of the two types of ion channels investigated. BK and L-type Ca2+ channels were colocalized in various compartments throughout the rat brain. Taken together, these results demonstrate a direct coassembly of BK channels and L-type Ca2+ channels in certain areas of the brain.