KChIP-like auxiliary subunits of Kv4 channels regulate excitability of muscle cells and control male turning behavior during mating in Caenorhabditis elegans.
J Neurosci
; 35(5): 1880-91, 2015 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-25653349
ABSTRACT
Voltage-gated Kv4 channels control the excitability of neurons and cardiac myocytes by conducting rapidly activating-inactivating currents. The function of Kv4 channels is profoundly modulated by K(+) channel interacting protein (KChIP) soluble auxiliary subunits. However, the in vivo mechanism of the modulation is not fully understood. Here, we identified three C. elegans KChIP-like (ceKChIP) proteins, NCS-4, NCS-5, and NCS-7. All three ceKChIPs alter electrical characteristics of SHL-1, a C. elegans Kv4 channel ortholog, currents by slowing down inactivation kinetics and shifting voltage dependence of activation to more hyperpolarizing potentials. Native SHL-1 current is completely abolished in cultured myocytes of Triple KO worms in which all three ceKChIP genes are deleted. Reexpression of NCS-4 partially restored expression of functional SHL-1 channels, whereas NCS-4(efm), a NCS-4 mutant with impaired Ca(2+)-binding ability, only enhanced expression of SHL-1 proteins, but failed to transport them from the Golgi apparatus to the cell membrane in body wall muscles of Triple KO worms. Moreover, translational reporter revealed that NCS-4 assembles with SHL-1 K(+) channels in male diagonal muscles. Deletion of either ncs-4 or shl-1 significantly impairs male turning, a behavior controlled by diagonal muscles during mating. The phenotype of the ncs-4 null mutant could be rescued by reexpression of NCS-4, but not NCS-4(efm), further emphasizing the importance of Ca(2+) binding to ceKChIPs in regulating native SHL-1 channel function. Together, these data reveal an evolutionarily conserved mechanism underlying the regulation of Kv4 channels by KChIPs and unravel critical roles of ceKChIPs in regulating muscle cell excitability and animal behavior in C. elegans.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Proteínas Sensoras de Cálcio Neuronal
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Proteínas Interatuantes com Canais de Kv
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Canais de Potássio Shal
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Locomoção
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article