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Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats

Year 2022, Volume: 39 Issue: 3, 868 - 873, 30.08.2022

Abstract

The purpose of this study was to look into the effects of pinacidil and glibenclamide on HCN1, KCNT1, Kir 6.1, and SUR1 gene expression in epileptic rats hippocampus and cortex.
Male Wistar-Albino rats were used in this study. The drugs pinacidil and glibenclamide were utilized. Control, Epilepsy, Epilepsy-O, and Epilepsy-B were the five groups formed. The epileptic focus was created by intracortical administration of penicillin at a dose of 500 IU/2 μl. Hippocampus and Cortex are removed from all animals and Kir 6.1, SUR1, HCN1, and KCNT1 gene expression levels were determined by qPCR. The SPSS 21 program was used for statistics.
HCN1 gene expression level is equal in the hippocampus and cortex (p<0.05). KCNT1, SUR1, and KIR6.1 are more expressed in the hippocampus than in the cortex (p<0.05). In epilepsy groups, HCN1 gene expression level was found to be higher than KCNT1, SUR1, and KIR6.1 gene expression levels (p<0.05). KIR6.1, SUR1, gene expression levels decreased with the application of pinacidil and glibenclamide (p<0.05). SUR1 and KIR6.1 gene expression levels were considerably lower in the epilepsy pinacidil group compared to the other groups. The gene expression levels in the hippocampus were found to be considerably higher than in the cortex group, according to this study. The fact that HCN1 gene expression levels are significantly greater in both the brain and the hippocampus 24 hours following the commencement of epileptic convulsions suggests that preventive medication may be possible.

Supporting Institution

This study was financed by the Abant İzzet Baysal University Research Foundation

Project Number

(BAP-grant number: 2019.10.01.1408).

References

  • 1 Devinsky O, Vezzani A, O’Brien TJ, Jette N, Scheffer IE, Curtis M, et al. Epilepsy. Nat Rev Dis Prim. 2018;4(May):18024.
  • 2 Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019;393(10172):689-701. 3 Akyuz E, Polat AK, Eroglu E, Kullu I, Angelopoulou E, Paudel YN. Revisiting the role of neurotransmitters in epilepsy: An updated review. Life Sci. 2021;265(November 2020):118826.
  • 4 Hofmann F, Biel M KU. International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev. 2005;57(4):455-462.
  • 5 Santoro B, Shah MM. Hyperpolarization-activated cyclic nucleotide-gated channels as drug targets for neurological disorders. Annu Rev Pharmacol Toxicol. 2020;60:109-131.
  • 6 Notomi T, Shigemoto R. Immunohistochemical Localization of Ih Channel Subunits, HCN1-4, in the Rat Brain. J Comp Neurol. 2004;471(3):241-276. doi:10.1002/cne.11039
  • 7 Jackson HA, Marshall CR, Accili EA. Evolution and structural diversification of hyperpolarization-activated cyclic nucleotide-gated channel genes. Physiol Genomics. 2007;29(3):231-245.
  • 8 Lainez S, Tsantoulas C, Biel M, McNaughton PA. HCN3 ion channels: roles in sensory neuronal excitability and pain. J Physiol. 2019;597(17):4661-4675.
  • 9 Seo H, Seol MJ, Lee K. Differential expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits during hippocampal development in the mouse. Mol Brain. 2015;8(1):1-14.
  • 10 Rivolta I, Binda A, Masi A, DiFrancesco JC. Cardiac and neuronal HCN channelopathies. Pflugers Arch Eur J Physiol. 2020;472(7):931-951.
  • 11 Brewster A, Bender RA, Chen Y, Dube C, Eghbal-Ahmadi M, Baram TZ. Developmental Febrile Seizures Modulate Hippocampal Gene Expression of Hyperpolarization-Activated Channels in an Isoform- and Cell-Specific Manner. J Neurosci. 2002;22(11):4591-4599.
  • 12 Tang B, Sander T, Craven KB, Hempelmann A, Escayg A. Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy. Neurobiol Dis. 2008;29(1):59-70.
  • 13 Jung S, Jones TD, Lugo JN, Sheerin AH, Miller JW, D’Ambrosio R, et al. Progressive dendritic HCN channelopathy during epileptogenesis in the rat pilocarpine model of epilepsy. J Neurosci. 2007;27(47):13012-13021.
  • 14 Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet. 2012;44(11):1255-1259.
  • 15 Nichols CG. KATP channels as molecular sensors of cellular metabolism. Nature. 2006;440(7083):470-476.
  • 16 Cole WC, McPherson CD, Sontag D. ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage. Circ Res. 1991;69(3):571-581.
  • 17 Wind T, Prehn JHM, Peruche B, Krieglstein J. Activation of ATP-sensitive potassium channels decreases neuronal injury caused by chemical hypoxia. Brain Res. 1997;751(2):295-299.
  • 18 Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev. 1999;20(2):101-135.
  • 19 D’Adamo MC, Catacuzzeno L, di Giovanni G, Franciolini F, Pessia M. K+ channelepsy: Progress in the neurobiology of potassium channels and epilepsy. Front Cell Neurosci. 2013;7(SEP):1-21.
  • 20 Kuisle M, Wanaverbecg N, Brewster AL, Frere SGA, Pinaultet D, Baram TZ, et al. Functional stabilization of weakened thalamic pacemaker channel regulation in rat absence epilepsy. J Physiol. 2006;575(1):83-100.
  • 21 Takanari H, Honjo H, Takemoto Y, Suzuki T, Kato S, Harada M, et al. Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling. J Pharmacol Sci. 2011;115(1):15-26.
  • 22 Xue Y, Xie N, Lin Y, Xu J, Han Y, Wang S, et al. Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures. Brain Res. 2011;1383:135-140.
  • 23 Ghasemi M, Shafaroodi H, Karimollah AR, Gholipour T, Nezami BG, Ebrahimi F, et al. ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. Seizure. 2010;19(1):53-58.
  • 24 Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross H, Elger CE, et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-482.
  • 25 Riechmann J, Strzelczyk A, Reese JP, Boor R, Stephani U, Langner C, et al. Costs of epilepsy and cost-driving factors in children, adolescents, and their caregivers in Germany. Epilepsia. 2015;56(9):1388-1397.
  • 26 Aaberg KM, Gunnes N, Bakken IJ, Søraas CL, Berntsen A, Magnus P, et al. Incidence and prevalence of childhood epilepsy: A nationwide cohort study. Pediatrics. 2017;139(5).
  • 27 Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disord. 2015;17(2):117-123.
  • 28 Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology. 2017;88(6):296-303.
  • 29 Saxena S, Li S. Defeating epilepsy: A global public health commitment. Epilepsia Open. 2017;2(2):153-155.
  • 30 Biel M, Wahl-Schott C, Michalakis S, Zong X. Hyperpolarization-activated cation channels: From genes to function. Physiol Rev. 2009;89(3):847-885.
  • 31 Bhattacharjee A, Kaczmarek LK. For K+ channels, Na+ is the new Ca2+. Trends Neurosci. 2005;28(8):422-428.
  • 32 Milligan CJ, Li M, Gazina EV, Heron SE, Nair U, Trager C, et al. KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. Ann Neurol. 2014;75(4):581-590.
  • 33 Ashcroft SJH, Ashcroft FM. Properties and functions of ATP-sensitive K-channels. Cell Signal. 1990;2(3):197-214.
  • 34 Heurteaux C, Lauritzen I, Widmann C LM. Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci U S A. 1995;92(May):4666-4670.
  • 35 Thomzig A, Prüss H, Veh RW. The Kir6.1-protein, a pore-forming subunit of ATP-sensitive potassium channels, is prominently expressed by giant cholinergic interneurons in the striatum of the rat brain. Brain Res. 2003;986(1-2):132-138.
  • 36 Lee K, Dixon AK, Freeman TC, Richardson PJ. Identification of an ATP-sensitive potassium channel current in rat striatal cholinergic interneurones. J Physiol. 1998;510(2):441-453.
Year 2022, Volume: 39 Issue: 3, 868 - 873, 30.08.2022

Abstract

Project Number

(BAP-grant number: 2019.10.01.1408).

References

  • 1 Devinsky O, Vezzani A, O’Brien TJ, Jette N, Scheffer IE, Curtis M, et al. Epilepsy. Nat Rev Dis Prim. 2018;4(May):18024.
  • 2 Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet. 2019;393(10172):689-701. 3 Akyuz E, Polat AK, Eroglu E, Kullu I, Angelopoulou E, Paudel YN. Revisiting the role of neurotransmitters in epilepsy: An updated review. Life Sci. 2021;265(November 2020):118826.
  • 4 Hofmann F, Biel M KU. International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev. 2005;57(4):455-462.
  • 5 Santoro B, Shah MM. Hyperpolarization-activated cyclic nucleotide-gated channels as drug targets for neurological disorders. Annu Rev Pharmacol Toxicol. 2020;60:109-131.
  • 6 Notomi T, Shigemoto R. Immunohistochemical Localization of Ih Channel Subunits, HCN1-4, in the Rat Brain. J Comp Neurol. 2004;471(3):241-276. doi:10.1002/cne.11039
  • 7 Jackson HA, Marshall CR, Accili EA. Evolution and structural diversification of hyperpolarization-activated cyclic nucleotide-gated channel genes. Physiol Genomics. 2007;29(3):231-245.
  • 8 Lainez S, Tsantoulas C, Biel M, McNaughton PA. HCN3 ion channels: roles in sensory neuronal excitability and pain. J Physiol. 2019;597(17):4661-4675.
  • 9 Seo H, Seol MJ, Lee K. Differential expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits during hippocampal development in the mouse. Mol Brain. 2015;8(1):1-14.
  • 10 Rivolta I, Binda A, Masi A, DiFrancesco JC. Cardiac and neuronal HCN channelopathies. Pflugers Arch Eur J Physiol. 2020;472(7):931-951.
  • 11 Brewster A, Bender RA, Chen Y, Dube C, Eghbal-Ahmadi M, Baram TZ. Developmental Febrile Seizures Modulate Hippocampal Gene Expression of Hyperpolarization-Activated Channels in an Isoform- and Cell-Specific Manner. J Neurosci. 2002;22(11):4591-4599.
  • 12 Tang B, Sander T, Craven KB, Hempelmann A, Escayg A. Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy. Neurobiol Dis. 2008;29(1):59-70.
  • 13 Jung S, Jones TD, Lugo JN, Sheerin AH, Miller JW, D’Ambrosio R, et al. Progressive dendritic HCN channelopathy during epileptogenesis in the rat pilocarpine model of epilepsy. J Neurosci. 2007;27(47):13012-13021.
  • 14 Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nat Genet. 2012;44(11):1255-1259.
  • 15 Nichols CG. KATP channels as molecular sensors of cellular metabolism. Nature. 2006;440(7083):470-476.
  • 16 Cole WC, McPherson CD, Sontag D. ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage. Circ Res. 1991;69(3):571-581.
  • 17 Wind T, Prehn JHM, Peruche B, Krieglstein J. Activation of ATP-sensitive potassium channels decreases neuronal injury caused by chemical hypoxia. Brain Res. 1997;751(2):295-299.
  • 18 Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev. 1999;20(2):101-135.
  • 19 D’Adamo MC, Catacuzzeno L, di Giovanni G, Franciolini F, Pessia M. K+ channelepsy: Progress in the neurobiology of potassium channels and epilepsy. Front Cell Neurosci. 2013;7(SEP):1-21.
  • 20 Kuisle M, Wanaverbecg N, Brewster AL, Frere SGA, Pinaultet D, Baram TZ, et al. Functional stabilization of weakened thalamic pacemaker channel regulation in rat absence epilepsy. J Physiol. 2006;575(1):83-100.
  • 21 Takanari H, Honjo H, Takemoto Y, Suzuki T, Kato S, Harada M, et al. Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling. J Pharmacol Sci. 2011;115(1):15-26.
  • 22 Xue Y, Xie N, Lin Y, Xu J, Han Y, Wang S, et al. Role of PI3K/Akt in diazoxide preconditioning against rat hippocampal neuronal death in pilocarpine-induced seizures. Brain Res. 2011;1383:135-140.
  • 23 Ghasemi M, Shafaroodi H, Karimollah AR, Gholipour T, Nezami BG, Ebrahimi F, et al. ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. Seizure. 2010;19(1):53-58.
  • 24 Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross H, Elger CE, et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-482.
  • 25 Riechmann J, Strzelczyk A, Reese JP, Boor R, Stephani U, Langner C, et al. Costs of epilepsy and cost-driving factors in children, adolescents, and their caregivers in Germany. Epilepsia. 2015;56(9):1388-1397.
  • 26 Aaberg KM, Gunnes N, Bakken IJ, Søraas CL, Berntsen A, Magnus P, et al. Incidence and prevalence of childhood epilepsy: A nationwide cohort study. Pediatrics. 2017;139(5).
  • 27 Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disord. 2015;17(2):117-123.
  • 28 Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology. 2017;88(6):296-303.
  • 29 Saxena S, Li S. Defeating epilepsy: A global public health commitment. Epilepsia Open. 2017;2(2):153-155.
  • 30 Biel M, Wahl-Schott C, Michalakis S, Zong X. Hyperpolarization-activated cation channels: From genes to function. Physiol Rev. 2009;89(3):847-885.
  • 31 Bhattacharjee A, Kaczmarek LK. For K+ channels, Na+ is the new Ca2+. Trends Neurosci. 2005;28(8):422-428.
  • 32 Milligan CJ, Li M, Gazina EV, Heron SE, Nair U, Trager C, et al. KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine. Ann Neurol. 2014;75(4):581-590.
  • 33 Ashcroft SJH, Ashcroft FM. Properties and functions of ATP-sensitive K-channels. Cell Signal. 1990;2(3):197-214.
  • 34 Heurteaux C, Lauritzen I, Widmann C LM. Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci U S A. 1995;92(May):4666-4670.
  • 35 Thomzig A, Prüss H, Veh RW. The Kir6.1-protein, a pore-forming subunit of ATP-sensitive potassium channels, is prominently expressed by giant cholinergic interneurons in the striatum of the rat brain. Brain Res. 2003;986(1-2):132-138.
  • 36 Lee K, Dixon AK, Freeman TC, Richardson PJ. Identification of an ATP-sensitive potassium channel current in rat striatal cholinergic interneurones. J Physiol. 1998;510(2):441-453.
There are 35 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Clinical Research
Authors

Ümit Kılıç 0000-0001-9917-0648

Hayriye Soytürk 0000-0002-0000-3768

Project Number (BAP-grant number: 2019.10.01.1408).
Early Pub Date August 30, 2022
Publication Date August 30, 2022
Submission Date July 1, 2022
Acceptance Date July 5, 2022
Published in Issue Year 2022 Volume: 39 Issue: 3

Cite

APA Kılıç, Ü., & Soytürk, H. (2022). Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats. Journal of Experimental and Clinical Medicine, 39(3), 868-873.
AMA Kılıç Ü, Soytürk H. Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats. J. Exp. Clin. Med. August 2022;39(3):868-873.
Chicago Kılıç, Ümit, and Hayriye Soytürk. “Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats”. Journal of Experimental and Clinical Medicine 39, no. 3 (August 2022): 868-73.
EndNote Kılıç Ü, Soytürk H (August 1, 2022) Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats. Journal of Experimental and Clinical Medicine 39 3 868–873.
IEEE Ü. Kılıç and H. Soytürk, “Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats”, J. Exp. Clin. Med., vol. 39, no. 3, pp. 868–873, 2022.
ISNAD Kılıç, Ümit - Soytürk, Hayriye. “Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats”. Journal of Experimental and Clinical Medicine 39/3 (August 2022), 868-873.
JAMA Kılıç Ü, Soytürk H. Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats. J. Exp. Clin. Med. 2022;39:868–873.
MLA Kılıç, Ümit and Hayriye Soytürk. “Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats”. Journal of Experimental and Clinical Medicine, vol. 39, no. 3, 2022, pp. 868-73.
Vancouver Kılıç Ü, Soytürk H. Investigation of the Effects of Pinacidil and Glibenclamide Administration on HCN1, KCNT1, Kir 6.1, SUR1 Gene Expressions in Hippocampus and Cortex Regions in Epileptic Rats. J. Exp. Clin. Med. 2022;39(3):868-73.