Decrease of inward rectification as a mechanism for arachidonic acid-induced potentiation of hKir2.3

Previously, we showed that arachidonic acid (AA) potentiates currents flowing through a cloned human inwardly rectifying K(+) channel, hKir2.3. The mechanism by which this potentiation occurs is not understood. Here, we report that this potentiation is mediated by multiple mechanisms and that one of them, which we studied in more detail, is consistent with AA-induced decrease of inward rectification. AA (10 micro M) potentiation of hKir2.3 whole-cell current increased with depolarization (40% greater at -47 mV than at -127 mV) and decreased with elevated extracellular [K(+)] (158+/-21%, 56+/-8% and 38+/-9% in 5.4, 70 and 135 mM K(+), respectively). Hyperpolarization elicited inward currents consisting of an instantaneous and two time-dependent components with time constants (at -97 mV) of 6.4+/-1.1 ms and 27.8+/-4.1 ms, respectively. AA (10 microM) significantly decreased the slow time constant (14.1+/-0.7 ms). Consistent with the kinetic changes, AA (10 microM) right-shifted the voltage dependence of the chord conductance (mid-point shifted by +9 mV). In inside-out patches where inward rectification was minimal, AA potentiation (38+/-3%) was smaller than in whole-cell recording and was not voltage dependent. These results are consistent with the idea that AA potentiates hKir2.3 in part by decreasing inward rectification of the channel.