ERG Channels Contribute to the Excitability of Pyramidal Neurons in Hippocampal CA1
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https://doi.org/10.5152/eurjther.2021.20061Keywords:
ERG channels, excitability, hippocampus, neurophysiology, electrophysiologyAbstract
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 dofetilide 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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References
Warmke JW, Ganetzky B. A family of potassium channel genes related to EAG in Drosophila and mammals. Proc Natl Acad Sci
USA. 1994;91(8):3438-3442.
Schwarz JR, Bauer CK. Functions of erg Kþ channels in excitable cells. J Cell Mol Med. 2004;8(1):22-30.
Pessia M, Servettini I, Panichi R, et al. ERG voltage-gated Kþ channels regulate excitability and discharge dynamics of the medial
vestibular nucleus neurones. J Physiol. 2008;586(20):4877-4890.
Hardman RM, Forsythe ID. Ether-a-go-go-related gene Kþ channels contribute to threshold excitability of mouse auditory
brainstem neurons. J Physiol. 2009;587(Pt. 11):2487-2497.
Niculescu D, Hirdes W, Hornig S, et al. Erg potassium currents of neonatal mouse Purkinje cells exhibit fast gating kinetics and are
inhibited by mGluR1 activation. J Neurosci. 2013;33(42):16729-16740.
Yildirim C, Bal R. ERG channels regulate excitability in stellate and bushy cells of mice ventral cochlear nucleus. J Membr Biol.
;251(5-6):711-722.
Doyle DA, Morais Cabral J, Pfuetzner R, et al. The structure of the potassium channel: Molecular basis of Kþ conduction and selectivity. Science. 1998;280(5360):69-77.
Vandenberg JI, Torres AM, Campbell TJ, et al. The HERG Kþ channel: Progress in understanding the molecular basis of its unusual
gating kinetics. Eur Biophys J. 2004;33(2):89-97.
Shepard PD, Canavier CC, Levitan ES. Ether-a-go-go-related gene potassium channels: What’s all the buzz about? Schizophr Bull.
;33(6):1263-1269.
Grizel AV, Glukhov GS, Sokolova OS. Mechanisms of activation of voltage-gated potassium channels. Acta Nat. 2014;6(4):10-26.
Sigworth FJ. Voltage gating of ion channels. Q Rev Biophys. 1994;27(1):1-40.
Johnston D, Hoffman DA, Magee JC, et al. Dendritic potassium channels in hippocampal pyramidal neurons. J Physiol. 2000;525
(Pt 1):75-81.
Guasti L, Cilia E, Crociani O, et al. Expression pattern of the ether-ago-go-related (ERG) family proteins in the adult mouse central
nervous system: Evidence for coassembly of different subunits. J Comp Neurol. 2005;491(2):157-174.
Fano S, Caliskan G, Heinemann U. Differential effects of blockade of ERG channels on gamma oscillations and excitability in rat hippocampal slices. Eur J Neurosci. 2012;36(12):3628-3635.
Saganich MJ, Machado E, Rudy B. Differential expression of genes encoding subthreshold-operating voltage-gated Kþ channels in
brain. J Neurosci. 2001;21(13):4609-4624.
Bal R, Baydas G. Electrophysiological properties of octopus neurons of the cat cochlear nucleus: an in vitro study. J Assoc Res Otolaryngol. 2009;10(2):281-293.
Bal R, Oertel D. Hyperpolarization-activated, mixed-cation current (I(h)) in octopus cells of the mammalian cochlear nucleus. J Neurophysiol. 2000;84(2):806-817.
Bal R, Oertel D. Potassium currents in octopus cells of the mammalian cochlear nucleus. J Neurophysiol. 2001;86(5):2299-2311.
Bal R, Oertel D. Hyperpolarization-activated, mixed-cation current (I-h) in octopus cells of the mammalian cochlear nucleus
(vol 84, pg 806, 2000). J Neurophysiol. 2004;92(2):1263.
Bal R, Oertel D. Voltage-activated calcium currents in octopus cells of the mouse cochlear nucleus. J Assoc Res Otolaryngol.
;8(4):509-521.
Bal R, Ozturk G, Etem EO, et al. Modulation of excitability of stellate neurons in the ventral cochlear nucleus of mice by ATPsensitive
potassium channels. J Membr Biol. 2018;251(1):163-178.
Yıldırım C, Ramazan B. Biophysical properties of ERG channels in octopus neurons of ventral cochlear nucleus. Eur J Ther.
;25(2):135-141.
Bal R, Ozturk G, Etem EO, et al. Modulation of the excitability of stellate neurons in the ventral cochlear nucleus of mice by TRPM2
channels. Eur J Pharmacol. 2020;882:173163.
Graves AR, Moore SJ, Bloss E, et al. Hippocampal pyramidal neurons comprise two distinct cell types that are countermodulated
by metabotropic receptors. Neuron. 2013;77(2):376.
Sacco T, Bruno A, Wanke E, et al. Functional roles of an ERG current isolated in cerebellar Purkinje neurons. J Neurophysiol.
;90(3):1817-1828.
Hirdes W, Schweizer M, Schuricht KS, et al. Fast erg K+ currents in rat embryonic serotonergic neurones. J Physiol. 2005;564(Pt 1):33-
]
Bauer CK, Schwarz JR.. Ether-a-go-go K(±) channels: Effective modulators of neuronal excitability. J Physiol. 2018;596(5):769-783.
Schwarz JR, Bauer CK. The ether-a-go-go-related gene K(þ) current: Functions of a strange inward rectifier. News Physiol Sci.
;14:135-142.
Chiesa N, Rosati B, Arcangeli A, et al. A novel role for the HERG K+channels: Spike-frequency adaptation. J Physiol.-London.
;502(3):715.
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