The Small Molecule NS11021 Is a Potent and Specific Activator of Ca2+-Activated Big-Conductance K+ Channels

• DOI: 10.1124/mol.107.038331
• Publication Date: 2007-07-17T00:41:16Z
• Authors: Bo Hjorth Bentzen; Antonio Nardi; Kirstine Calloe; Lars Siim Madsen; Søren-Peter Olesen; Morten Grunnet
• Keywords: Mice, Knockout; 0301 basic medicine; Guinea Pigs; Thiourea; Tetrazoles; Cell Line; Mitochondria; 3. Good health; Mice; Xenopus laevis; 03 medical and health sciences; Animals; Humans; Calcium; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits

Large-conductance Ca²⁺- and voltage-activated K⁺ channels (Kca1.1/BK/MaxiK) are widely expressed ion channels. They provide a Ca²⁺-dependent feedback mechanism for the regulation of various body functions such as blood flow, neurotransmitter release, uresis, immunity. In addition, mitochondrial channel with KCa1.1-resembling properties has been found in heart, where it may be involved energy consumption. present study, effect novel NeuroSearch compound, 1-(3,5-bis-trifluoromethyl-phenyl)-3-[4-bromo-2-(1<i>H</i>-tetrazol-5-yl)-phenyl]-thiourea (NS11021), was investigated on cloned KCa1.1 <i>Xenopus laevis</i> oocytes mammalian cells using electrophysiological methods. NS11021 at concentrations above 0.3 μM activated concentration-dependent manner by parallel-shifting activation curves to more negative potentials. Single-channel analysis revealed that increased open probability altering gating kinetics without affecting single-channel conductance. (10 μM) influenced neither number Kv nor endogenous Na⁺ Ca²⁺ (L- T-type) guinea pig cardiac myocytes. conclusion, is activator better specificity 10 times higher potency compared most broadly applied opener, NS1619. Thus, might valuable tool compound when addressing physiological pathophysiological roles