SELECTIVE ACTIVATION OF CA2-ACTIVATED K+ CHANNELS BY CO-LOCALIZED CA2+ CHANNELS IN HIPPOCAMPAL-NEURONS()

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.