IndraLab

"DFNA2 is a progressive deafness caused by mutations in the voltage activated potassium channel KCNQ4."

"Like Kv7.4:CaM 1234 , Kv7.4:CaM 3 showed insensitivity to the changing intracellular calcium levels, and both varying free calcium concentrations of the pipette solutions and application of BAPTA-AM have no effect on the activation rate ( xref ; τ values at 40 mV: Kv7.4:CaM 3 pretreated with 20 μM BAPTA-AM = 19.6 ± 2.1 ms; Kv7.4:CaM 3 with 10 mM EGTA = 19.2 ± 1.6 ms; Kv7.4:CaM 3 with 10 mM EGTA plus 3 mM CaCl 2 = 17.9 ± 1.4 ms; Kv7.4:CaM 3 with 10 mM EGTA plus 6 mM CaCl 2 = 18.1 ± 2.2 ms) or the voltage-dependent activation ( xref ; V 1/2 values: Kv7.4:CaM 3 pretreated with 20 μM BAPTA-AM = −45.3 ± 1.5 mV; Kv7.4:CaM 3 with 10 mM EGTA = −47.3 ± 1.7 mV; Kv7.4:CaM 3 with 10 mM EGTA plus 3 mM CaCl 2 = −48.5 ± 1.2 mV; Kv7.4:CaM 3 with 10 mM EGTA plus 6 mM CaCl 2 = −47.1 ± 1.3 mV) of Kv7.4:CaM 3 ."

"In addition, mutations at both positions did not affect voltage activation of KCNQ4, suggesting that these residues directly affect SsTx-KCNQ4 interaction."

"However, both activation kinetics ( xref ; τ values at 40 mV: Kv7.4:CaM 1234 with 10 mM EGTA = 20.5 ± 2.5 ms; Kv7.4:CaM 1234 with 10 mM EGTA plus 3 mM CaCl 2 = 17.7 ± 2.6 ms; Kv7.4:CaM 1234 with 10 mM EGTA plus 6 mM CaCl 2 = 18.4 ± 2.2 ms) and voltage-dependent activation ( xref ; V 1/2 values at 40 mV: Kv7.4:CaM 1234 with 10 mM EGTA = −48.0 ± 1.4 mV; Kv7.4:CaM 1234 with 10 mM EGTA plus 3 mM CaCl 2 = −47.2 ± 1.8 mV; Kv7.4:CaM 1234 with 10 mM EGTA plus 6 mM CaCl 2 = −45.7 ± 1.1 mV) of Kv7.4:CaM 1234 remained unchanged when we used different pipette solutions."

"Also, both BMS-204352 and retigabine potentiated the voltage activated KCNQ4 current at all potentials tested."