Hippocampal A-type current and Kv4.2 channel modulation by the sulfonylurea compound NS5806

Protein-Ligand Interactions and Allosteric Regulation of Activity in DREAM Protein

“…Interaction of KChIP1, KChIP2, and KChIP3 with KV4 channels expressed in xenopus oocytes results in an increase in current density, acceleration of recovery from inactivation, and slower inactivation kinetics . Similar effects on the biophysical properties of neural fast inactivating K + currents have been observed for KChIP1 (Bourdeau et al 2011) and KChIP3 (Witzel, Fischer & Bähring 2012). …”

“…Interaction of KChIP2 with KV4 channels in the heart results in an increase in current density, acceleration of recovery from inactivation, and slower inactivation kinetics . Similar effects on the biophysical properties of neural fast inactivating K + currents have been observed for KChIP1 (Bourdeau et al 2011) and KChIP3 (Witzel, Fischer & Bähring 2012). Even though the molecular structures of the KV4 T1 domain in presence and absence of the regulatory KChIP1 is known, the mechanism by which these auxiliary proteins mediate channel gating remains unknown.…”

“…Interestingly, this ITO activator has also been shown to decrease ISA currents in cultured hippocampal neurons where its effects on gating kinetics are comparable to those observed in heart tissue (Witzel, Fischer & Bähring 2012).…”

“…Moreover, the induced potassium current modulation by NS5806 has been shown to depend on the presence of KV4 auxiliary KChIP protein (Witzel, Fischer & Bähring 2012). …”

“…The second binding site has a more polar character and contains residues located at the Nterminal domain (Scannevin et al 2004). In addition, the functional properties of the KChIP-Kv4 complexes have been observed to be modulated by association of small hydrophobic molecules, such as arachidonic acid (Holmqvist et al 2001) and NS5806 (Witzel, Fischer & Bähring 2012).…”