Nv. Marrion et Sj. Tavalin, SELECTIVE ACTIVATION OF CA2-ACTIVATED K+ CHANNELS BY CO-LOCALIZED CA2+ CHANNELS IN HIPPOCAMPAL-NEURONS(), Nature, 395(6705), 1998, pp. 900-905
Calcium entry through voltage-gated calcium channels can activate eith
er large- (BK) or small- (SK) conductance calcium-activated potassium
channels. In hippocampal neurons, activation of BK channels underlies
the falling phase of an action potential and generation of the fast af
terhyperpolarization (AHP)(1,2). In contrast, SK channel activation un
derlies generation of the slow AHP after a burst of action potentials(
3). The source of calcium for BK channel activation is unknown, but th
e slow AHP is blocked by dihydropyridine antagonists(4,5), indicating
that L-type calcium channels provide the calcium for activation of SK
channels. It is not understood how this specialized coupling between c
alcium and potassium channels is achieved, Here we study channel activ
ity in cell-attached patches from hippocampal neurons and report a uni
que specificity of coupling. L-type channels activate SK channels only
, without activating BK channels present in the same patch. The delay
between the opening of L-type channels and SK channels indicates that
these channels are 50-150 nm apart. In contrast, N-type calcium channe
ls activate BK channels only, with opening of the two channel types be
ing nearly coincident. This temporal association indicates that N and
BK channels are very close. Finally, P/Q-type calcium channels do not
couple to either SK or BK channels. These data indicate an absolute se
gregation of coupling between channels, and illustrate the functional
importance of submembrane calcium microdomains.