Furthermore, gating of RyR is modulated by membrane potential with steps to hyperpolarized or depolarized potentials of more than ∼40 mV causing an initial activation and then inactivation (191).
Membrane potential was stepped from −80 to +20 mV for 2 s followed by a 4-s step to −40 mV to elicit IHERG tails.
When the membrane potential was stepped to various potentials, the inward K+ currents were potentiated in the presence of 100 nM 5-HT.
Adaptation was no longer evident when the membrane potential was stepped to +86 mV (Fig. 7A, B), at which potential the currents in the mutant OHCs decayed quite slowly upon termination of the force step (Fig. 7B).
Figure 9D illustrates the rapid suppression of the current when the oocytes were exposed to Cu-Phen and stimulated by a train protocol where the membrane potential was stepped every 30 s to +30 mV.
When membrane potential was stepped every 30 sec from −90 to −50 mV, application of 10 µM and 50 µM of compound 15 produced 3.2- and 9.1-fold increase in current amplitude, respectively (n = 10; Figure 5B D).
In all whole-cell experiments the holding potential was −40 mV, periodically (once every 5 s) the membrane potential was stepped to −100 mV (for 30 ms) and a 200 ms voltage ramp to +100 mV was applied.
Input resistance (Rin) was measured by injecting several hyperpolarizing current steps, recording the response of the membrane potential to these steps, subtracting the resting membrane potential, and calculating Rin from linear current-voltage (I V) curve fitting.
For the IV curve of the KARs, the holding membrane potential was changed in steps of 20 mV from −60 mV to 40 mV and at each step, five responses were recorded.
After 1.5 min, membrane potential was varied in steps by sequential additions of cyanide (50 mM KCN in 0.5 M Hepes, pH 7.2; final concentrations 5 255 μM).
