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 alpha-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)beta(3) subunits with Slo(27) channels revealed rapid functional 
coupling. By contrast, extremely rare examples of rapid functional coupling were 
observed with co-expression of Ca(V)1.2/Ca(V)beta(3) and Slo(27) channels. 
Action potential repolarisation in hippocampal pyramidal neurons was slowed by 
the N-type channel blocker omega-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.