Signal Transduction–Dependent Channels

Abstract

From the moment the first member of this ion channel family, Slo1, was discovered, the scientific world was confronted with a molecular Pandora’s box: once opened, its electrical language left scientists bewitched. They were fascinated with this “monster” of a single-channel conductance (250 pS in symmetrical 100 mM K⁺) close to the ceiling imposed by simple diffusion combined with an exquisite K⁺ selectivity. Slo1 channels are essentially impermeable to Na⁺ and conduct K⁺ 10- and 200-fold more effectively than Rb⁺ and Cs⁺, respectively, though it was previously thought that large conductance channels were not supposed to be so selective. At the same time, the channel was activated by voltage and cytoplasmic Ca²⁺. This latter property led Meech in 1978 to hypothesize that this conductance system was perfect link between cell metabolism and electrical activity, and he was right on the mark¹. Because of its large conductance, this voltage- and calcium-activated K⁺ channel was christened “maxi-K” or “BK” (for big K⁺). This high single-channel conductance is not only a characteristic of Slo1 but is shared by the other members of this family of K⁺ channels, Slo2 and Slo3. These channels, although similar in many aspects to the voltage-gated K⁺ (Kv) channels, are more versatile in that their activation is modulated by ions, as is the case of Slo1. In the case of Slo2, the key modulatory ions are Na⁺ and Cl⁻ and in Slo3, H⁺ (pH).