TABLE 7

KCa4.1 channels

Channel name KCa4.1
Description Sodium-activated potassium channel, rat (Slack) ortholog gated by voltage and synergistically by internal Na+ and CI-
Other names Slack, Slo2.2, KCNT1
Molecular information Human: 1256aa NM_020822, chr. 9q34.3, KCNT1
Mouse: XM_622105 (predicted), chr. 2
Rat: 1237aa, NM_021853, chr. 3p13
Associated subunits Heteromeric association between rat Slack and Slo1,3 no β-subunits identified
Functional assays Voltage-clamp, patch-clamp
Current K+-selective
Conductance 25–65pS (Slack),3 60–180pS (Slack/Slo1 heteromeric channels)3; 88pS (80 mM symmetric K+), 165pS (160 mM symmetric K+), prominent multiple subconductance states (Slack)6
Ion selectivity K+-selective
Activation Gated by voltage (weakly voltage-sensitive) and synergistically by internal Na+ and CI- (half-maximal Na+ activation [Na+]0.5 = 15 mM with 160 mM CI-; half-maximal CI- activation [Cl-]0.5 = 8.1 mM with 80 mM Na+)6
Inactivation None
Activators None
Blockers TEA, >60% block by 20 mM2; quindine, >90% block by 1.0 mM2
Gating inhibitors Intracellular Ca+2 (5-fold reduction of NPo increasing Ca2+ from 0–3 μM)3
Radioligands None
Channel distribution Brain, testis, kidney (mouse Slo2.2)6; brain [brainstem (red nucleus, oculomotor nucleus, mesencephalic trigeminal, trapezoid nucleus, gigantocellularius, vestibular nucleus), olfactory bulb, frontal cortex, hippocampus], kidney, testis (rat Slack)1; neuronal immunohistochemical staining observed in cell bodies and axonal tracts
Physiological functions Not established
Mutations and pathophysiology Not established; C. elegans slo-2 loss-of-function mutants hypersensitive to hypoxic death5,6
Pharmacological significance Not established; native KNa channels proposed to protect against hypoxic insult in cardiac muscles4
Comments No published functional expression data for the human ortholog

  • aa, amino acids; chr., chromosome; TEA, tetraethylammonium.

  • ↵1. Bhattacharjee A, Gan L, and Kaczmarek LK (2002) Localization of the Slack potassium channel in the rat central nervous system. J Comp Neurol 454:241-254

  • ↵2. Bhattacharjee A, Joiner WJ, Wu M, Ynag Y, Sigworth FJ, and Kaczmarek LK (2003) Slick (Slo2.1), a rapidly-gated sodium-activated potassium channel inhibited by ATP. J Neurosci 23:11681-11691

  • ↵3. Joiner WJ, Tang MD, Wang LY, Dworetzky SI, Boissard CG, Gan L, Gribkoff VK, and Kaczmarek LK (1998) Formation of intermediate-conductance-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci 1:462-469

  • ↵4. Kameyama M, Kakei M, Sato R, Shibasaki T, Matsuda H, and Irisawa H (1984) Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature (Lond) 309:354-356

  • ↵5. Yuan A, Dourado M, Butler A, Walton N, Wei A, and Salkoff L (2000) SLO-2, A K+ channel with an unusual CI- dependence. Nat Neurosci 3:771-779

  • ↵6. Yuan A, Santi CM, Wei A, Wang Z-W, Pollak K, Nonet M, Kaczmarek L, Crowder CM, and Salkoff L (2003) The sodium-activated potassium channel is encoded by a member of the Slo gene family. Neuron 37:765-773