Co-assembly of N-type Ca 2+ and BK channels underlies functional coupling in rat brain

David J. Loane, Pedro A. Lima, Neil V. Marrion

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Abstract

Activation of large conductance Ca 2+ -activated potassium (BK) channels hastens action potential repolarisation and generates the fast afterhyperpolarisation in hippocampal pyramidal neurons. A rapid coupling of Ca 2+ entry with BK channel activation is necessary for this to occur, which might result from an identified coupling of Ca 2+ entry through N-type Ca 2+ channels to BK channel activation. This selective coupling was extremely rapid and resistant to intracellular BAPTA, suggesting that the two channel types are close. Using reciprocal co-immunoprecipitation, we found that N-type channels were more abundantly associated with BK channels than L-type channels (Ca v 1.2) in rat brain. Expression of only the pore-forming α-subunits of the N-type (Ca v 2.2) and BK (Slo 27 ) channels in a non-neuronal cell-line gave robust macroscopic currents and reproduced the interaction. Co-expression of Ca v 2.2/Ca v β3 subunits with Slo 27 channels revealed rapid functional coupling. By contrast, extremely rare examples of rapid functional coupling were observed with coexpression of Ca v 1.2/Ca v β 3 and Slo 27 channels. Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker ω-conotoxin GVIA, but not by the L-type channel blocker isradipine. These data showed that selective functional coupling between N-type Ca 2+ and BK channels provided rapid activation of BK channels in central neurons.

Original languageEnglish
Pages (from-to)985-995
Number of pages11
JournalJournal Of Cell Science
Volume120
Issue number6
DOIs
Publication statusPublished - 15 Mar 2007

Keywords

  • Action potential
  • Channel coupling
  • Co-immunoprecipitation
  • Hippocampus

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