Fluorescence-based Tl(+)-influx assays as a novel approach for characterization of small-conductance Ca(2+)-activated K (+) channel modulators.

Small-conductance Ca(2+)-activated potassium (SK) channels constitute a family of ion channels that are regulated by the cytosolic Ca(2+) concentration. Increases in the intracellular Ca(2+) concentration ([Ca(2+)](i)) result in opening of the channels, which in turn will lead to changes in the membrane potential. As the name implies, the channels are of small conductance, but even so, they are known to play a crucial role in several physiological processes, such as modulation of neurotransmitter and hormone secretion, as well as memory and learning (e.

Inhibitory gating modulation of small conductance Ca2+-activated K+ channels by the synthetic compound (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) reduces afterhyperpolarizing current in hippocampal CA1 neurons.

SK channels are small conductance Ca(2+)-activated K(+) channels important for the control of neuronal excitability, the fine tuning of firing patterns, and the regulation of synaptic mechanisms. The classic SK channel pharmacology has largely focused on the peptide apamin, which acts extracellularly by a pore-blocking mechanism. 1-Ethyl-2-benzimidazolinone (1-EBIO) and 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) have been identified as positive gating modulators that increase the apparent Ca(2+) sensitivity of SK channels.

The beta subunit determines the ion selectivity of the GABAA receptor.

The gamma-aminobutyric acid, type A (GABA(A)) receptor is a chloride-conducting receptor composed of alpha, beta, and gamma subunits assembled in a pentameric structure forming a central pore. Each subunit has a large extracellular agonist binding domain and four transmembrane domains (M1-M4), with the second transmembrane (M2) domain lining the pore. Mutation of five amino acids in the M1-M2 loop of the beta(3) subunit to the corresponding amino acids of the alpha(7) nicotinic acetylcholine subunit rendered the GABA(A) receptor cation-selective upon co-expression with wild type alpha(2) and gamma(2) subunits.