ERG Channels Contribute to the Excitability of Pyramidal Neurons in Hippocampal CA1

Objective: Ether-a-go-go-related genes (ERG; Kv11) include three different erg channels, namely, Kv11.1, Kv11.2, and Kv11.3 or ERG1, ERG2, and ERG3. The aim of this study is to investigate the effects of ERG channel blockers on the biophysical properties of pyramidal cells in the hippocampus CA1 area. Methods: The characterization of ERG currents was obtained using the whole cell configuration of the patch clamp technique. In the current clamp, we used selective ERG channel blockers (E-4031 (10 lM), dofetilide (1 lM), ergtoxin (200 nM), and terfenadine (10 lM)), which significantly incremented the input resistance of the pyramidal neurons (P < .05). All other ERG channel blockers except dofeti lide have significantly increased neuronal excitability of hippocampal CA1 pyramidal neurons (P < .05). They also increased the action potential (AP) firing rate of cells in response to a square current pulse (P < .05). Results: In the voltage clamp, the biophysical characteristic of ERG channels was determined by the measurement of tail currents. The E-4031-isolated current was observed at nearly –65 mV. The voltage-depended activation and inactivation curve of ERG channels was fitted with Boltzmann function, resulting in the V1/2 value of –48.95 mV, the slope factor of 4.54 mV and the V1/2 value of –77.35 mV, the slope factor of 10.58 mV, respectively. The exponential function is used to determine deactivation kinetics of ERG channels. It was observed that the rate of deactivation increased when the membrane potential was more hyperpolarized. Conclusion: In conclusion, both current and voltage clamp studies showed that ERG channels contribute to the modulation of excitability and frequency of AP in pyramidal neurons of the hippocampus in mice.

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