Transient receptor potential vanilloid 4 activation inhibits the delayed rectifier potassium channels in hippocampal pyramidal neurons: An implication in pathological changes following pilocarpine-induced status epilepticus.
J Neurosci Res
; 99(3): 914-926, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33393091
ABSTRACT
Activation of transient receptor potential vanilloid 4 (TRPV4) can increase hippocampal neuronal excitability. TRPV4 has been reported to be involved in the pathogenesis of epilepsy. Voltage-gated potassium channels (VGPCs) play an important role in regulating neuronal excitability and abnormal VGPCs expression or function is related to epilepsy. Here, we examined the effect of TRPV4 activation on the delayed rectifier potassium current (IK ) in hippocampal pyramidal neurons and on the Kv subunits expression in male mice. We also explored the role of TRPV4 in changes in Kv subunits expression in male mice following pilocarpine-induced status epilepticus (PISE). Application of TRPV4 agonists, GSK1016790A and 5,6-EET, markedly reduced IK in hippocampal pyramidal neurons and shifted the voltage-dependent inactivation curve to the hyperpolarizing direction. GSK1016790A- and 5,6-EET-induced inhibition of IK was blocked by TRPV4 specific antagonists, HC-067047 and RN1734. GSK1016790A-induced inhibition of IK was markedly attenuated by calcium/calmodulin-dependent kinase II (CaMKII) antagonist. Application of GSK1016790A for up to 1 hr did not change the hippocampal protein levels of Kv1.1, Kv1.2, or Kv2.1. Intracerebroventricular injection of GSK1016790A for 3 d reduced the hippocampal protein levels of Kv1.2 and Kv2.1, leaving that of Kv1.1 unchanged. Kv1.2 and Kv2.1 protein levels as well as IK reduced markedly in hippocampi on day 3 post PISE, which was significantly reversed by HC-067047. We conclude that activation of TRPV4 inhibits IK in hippocampal pyramidal neurons, possibly by activating CaMKII. TRPV4-induced decrease in Kv1.2 and Kv2.1 expression and IK may be involved in the pathological changes following PISE.
Palavras-chave
Kv subunit expression; RRID: SCR_003070 (ImageJ software); RRID: SCR_012763 (STATA software); RRID:AB_10673392 (Kv2.1 antibody); RRID:AB_2040144 (Kv1.1 antibody); RRID:AB_2313792 (Kv1.2 antibody); RRID:AB_2630358 (GAPDH antibody); hippocampus; pilocarpine-induced status epilepticus; transient receptor potential vanilloid 4; voltage-gated potassium channel
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estado Epiléptico
/
Células Piramidais
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Canais de Potássio de Retificação Tardia
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Canais de Cátion TRPV
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article