+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Low-Mg(2+) treatment increases sensitivity of voltage-gated Na(+) channels to Ca(2+)/calmodulin-mediated modulation in cultured hippocampal neurons

, : Low-Mg(2+) treatment increases sensitivity of voltage-gated Na(+) channels to Ca(2+)/calmodulin-mediated modulation in cultured hippocampal neurons. American Journal of Physiology. Cell Physiology 308(8): C594-C605

Culture of hippocampal neurons in low-Mg(2+) medium (low-Mg(2+) neurons) results in induction of continuous seizure activity. However, the underlying mechanism of the contribution of low Mg(2+) to hyperexcitability of neurons has not been clarified. Our data, obtained using the patch-clamp technique, show that voltage-gated Na(+) channel (VGSC) activity, which is associated with a persistent, noninactivating Na(+) current (INa,P), was modulated by calmodulin (CaM) in a concentration-dependent manner in normal and low-Mg(2+) neurons, but the channel activity was more sensitive to Ca(2+)/CaM regulation in low-Mg(2+) than normal neurons. The increased sensitivity of VGSCs in low-Mg(2+) neurons was partially retained when CaM12 and CaM34, CaM mutants with disabled binding sites in the N or C lobe, were used but was diminished when CaM1234, a CaM mutant in which all four Ca(2+) sites are disabled, was used, indicating that functional Ca(2+)-binding sites from either lobe of CaM are required for modulation of VGSCs in low-Mg(2+) neurons. Furthermore, the number of neurons exhibiting colocalization of CaM with the VGSC subtypes NaV1.1, NaV1.2, and NaV1.3 was significantly higher in low- Mg(2+) than normal neurons, as shown by immunofluorescence. Our main finding is that low-Mg(2+) treatment increases sensitivity of VGSCs to Ca(2+)/CaM-mediated regulation. Our data reveal that CaM, as a core regulating factor, connects the functional roles of the three main intracellular ions, Na(+), Ca(2+), and Mg(2+), by modulating VGSCs and provides a possible explanation for the seizure discharge observed in low-Mg(2+) neurons.


PMID: 25652447

DOI: 10.1152/ajpcell.00174.2014

Other references

Yasuno, Y.; Endo, T.; Makita, S.; Aoki, G.; Itoh, M.; Yatagai, T., 2006: Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation. We demonstrate 3-D optical coherence tomography using only 1-D mechanical scanning. This system uses the principle of Fourier domain optical coherence tomography for depth resolution, 1-D imaging for lateral vertical resolution, and mechanical sca...

Roumeguère, T.; Zouaoui Boudjeltia, K.; Hauzeur, C.; Schulman, C.; Vanhaeverbeek, M.; Wespes, E., 2009: Is there a rationale for the chronic use of phosphodiesterase-5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia?. To critically review the physiological roles of phosphodiesterase-5 (PDE5), to explain and support the putative impact and clinical significance of PDE5 inhibitors (PDE5-Is) in the treatment of lower urinary tract symptoms (LUTS) associated with b...

Wallin, A.; Blennow, K., 1996: Clinical subgroups of the Alzheimer syndrome. During the last decade, senile dementia and the presenile disease that was named after Alois Alzheimer have been considered a single entity called Alzheimer's disease (AD). This same decade has witnessed the development of many diagnostic too...

Clemente R.; Nagar D.; Lindeman R.D.; Wathen R.L., 1981: Myo globinuric acute renal failure associated with chronic ethanol abuse. Kidney International 19(1): 123

Sano, T.G.; Hayakawa, H., 2014: Roles of dry friction in the fluctuating motion of an adiabatic piston. The motion of an adiabatic piston under dry friction is investigated to clarify the roles of dry friction in nonequilibrium steady states. We clarify that dry friction can reverse the direction of the piston motion and causes a discontinuity or a...

Wang, S.; Yang, J.; Cai, Q., 2001: Biomaterial and cells scaffold for tissue engineering uses. Zhonghua Zheng Xing Wai Ke Za Zhi 16(6): 328-330

Willmer C.M.; Petropoulou Y.; Manetas Y., 1990: No light activation and high malate sensitivity of phosphoenolpyruvate carboxylase in guard cell protoplasts of commelina communis l. Guard cell protoplasts (GCP) were prepared from leaves of Commelina communis L. and phosphoenolpyruvate carboxylase (PEPc) activity recorded after injection of the protoplasts directly into the assay medium. The GCP were lysed immediately by the p...

Ryan T.P.; Bumpus J.A., 1989: Biodegradation of 2 4 5 t in liquid culture and in soil by the white rot fungus phanerochaete chrysosporium. Extensive biodegratation of [14C]-2,4,5-trichlorophenoxyacetic acid ([14C]-2,4,5-T) by the white rot fungus Phanerochaete chrysosporium was demonstrated in nutrient nitrogen-limited aqueous cultures in [14C]-2,4,5-T-contaminated soil inoculated wi...

Koniukhov, B.V., 1971: Action of genes in the ontogenesis of vertebrates. Uspekhi Sovremennoi Biologii 71(1): 107-122

Torra, M.; Barrot, C.; Ortega, M.; Sanchez, C.; Xifro, A.; Corbella, J.; Gene, M., 2006: Genetic variability of delta-aminolevulinic acid dehydratase (delta-ALA) and the whole blood lead concentration in Northeast Spain. The second enzyme of the heme-biosynthetic pathway, delta-aminolevulinic acid dehydratase (ALAD), is a cytosolic enzyme that catalyzes the condensation of two molecules of 5-aminolevulinate (ALA) to form porphobilinogen. The gene that encodes this...