Vasa recta voltage-gated Na+ channel Nav1.3 is regulated by calmodulin.

  title={Vasa recta voltage-gated Na+ channel Nav1.3 is regulated by calmodulin.},
  author={Whaseon Lee‐Kwon and Jae Hwan Goo and Zhong Zhang and Erik P. Silldorff and Thomas L. Pallone},
  journal={American journal of physiology. Renal physiology},
  volume={292 1},
Rat descending vasa recta (DVR) express a tetrodotoxin (TTX)-sensitive voltage-operated Na(+) (Na(V)) conductance. We examined expression of Na(V) isoforms in DVR and tested for regulation of Na(V) currents by calmodulin (CaM). RT-PCR in isolated permeabilized DVR using degenerate primers targeted to TTX-sensitive isoforms amplified a product whose sequence identified only Na(V)1.3. Immunoblot of outer medullary homogenate verified Na(V)1.3 expression, and fluorescent immunochemistry showed Na… 

Figures from this paper

Voltage-gated divalent currents in descending vasa recta pericytes.

DVR pericytes predominantly express voltage-gated divalent currents that are carried by L- type channels, consistent with "long-lasting" L-type Ca(V).

Descending vasa recta endothelia express inward rectifier potassium channels.

It is concluded that strong, inwardly rectifying K(IR)2.x isoforms are expressed in DVR and mediate K(+)-induced hyperpolarization of the endothelium.

Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat.

It is concluded that endothelial responses may offset the ability of acute ouabain exposure to enhance DVR vasoconstriction and lead to hypertension and DVR endothelial dysfunction, manifested as reduced [Ca(2+)](CYT) responses to both oUabain- and endothelium-dependent vasodilators.

Voltage-dependent inward currents in smooth muscle cells of skeletal muscle arterioles

The results suggest that Na+ and at least two types (T- and L-) of Ca2+ voltage-gated channels contribute to depolarization of smooth muscle cells in skeletal muscle arterioles.

Mural propagation of descending vasa recta responses to mechanical stimulation.

It is concluded that DVR are mechanosensitive and that rapid transmission of signals along the vessel axis requires participation of gap junctions, L-type Ca²⁺ channels, and pericyte depolarization.

Role of calmodulin and myosin light chain kinase in the activation of carbachol-activated cationic current in murine ileal myocytes.

It is suggested that the classical type transient receptor potential (TRPC) channel 5 might be a candidate for nonselective cationic currents (NSCC) activated by muscarinic stimulation in gastrointestinal smooth muscle cells.

Properties of Calmodulin Binding to NaV1.2 IQ Motif and Its Autism-Associated Mutation R1902C

The binding ability of CaM and CaM's constituent proteins including N- and C lobe to the IQ motif of NaV1.2 and its mutant was investigated by protein pull-down experiments and it was discovered that the combination between Ca2+/calmodulin and theIQ motif was U-shaped with the highest at [Ca2+] ≈ free and the lowest at 100 nM [Ca 2+].

The modulation of the excitability of primary sensory neurons by Ca2+–CaM–CaMKII pathway

Investigations show that the excitability of capsaicin sensitive small and medium TG neurons can be regulated by Ca2+–CaM–CaMKII pathway through modulating VGSCs and VGPCs.



Control of descending vasa recta pericyte membrane potential by angiotensin II.

It is concluded that ANG II activates a Ca(2+)-dependent Cl(-) conductance in OMDVR pericytes to induce membrane depolarization and Psi m oscillations.

KATP channel conductance of descending vasa recta pericytes.

It is concluded that DVR pericytes express K(ATP) channels that make a significant contribution to basal K(+) conductance and are inhibited by ANG II and endothelin-1.

Membrane potential controls calcium entry into descending vasa recta pericytes.

The conclusion that DVR vasoreactivity is controlled through variation of membrane potential and voltage-gated Ca(2+) entry into the pericyte cytoplasm is supported.

TTX-sensitive voltage-gated Na+ channels are expressed in mesenteric artery smooth muscle cells.

The present study indicates that TTX-sensitive, voltage-gated Na+ channels are present in SMCs from the rat and mouse mesenteric artery, and the presence of these channels in freshly isolated SMC depends critically on the enzymatic dissociation conditions.

Electrophysiological and molecular identification of voltage‐gated sodium channels in murine vascular myocytes

The molecular identity of the voltage‐gated Na+ channel in freshly dispersed smooth muscle cells is established for the first time and it is shown that these channels can modulate contractility through a novel mechanism of action possibly involving reverse mode Na+–Ca2+ exchange.

Regulation of Ca2+ homeostasis by atypical Na+ currents in cultured human coronary myocytes.

I(Na) regulates [Ca2+]i in primary cultured HCMs, effective at baseline, involves a tonic control of Ca2+ influx via depolarization-gated Ca2- channels and, to a lesser extent, via a Na+/Ca2- exchanger working in the reverse mode.

Ouabain augments Ca(2+) transients in arterial smooth muscle without raising cytosolic Na(+).

Results suggest that Na(+) enters a tiny cytosolic space between the plasmalemma (PL) and the adjacent sarcoplasmic reticulum (SR) via an Mg(2+)- and La(3+)-blockable mechanism that is activated by SR store depletion.

Human Saphenous Vein Endothelial Cells Express a Tetrodotoxin-resistant, Voltage-gated Sodium Current*

Results suggest that TTX-resistant Na+ channels of the hH1 isoform are expressed in human saphenous vein endothelium and that the presence of these channels is controlled by a serum factor.

Calmodulin Binds to the C Terminus of Sodium Channels Nav1.4 and Nav1.6 and Differentially Modulates Their Functional Properties

It is demonstrated that CaM can regulate the properties of VGSCs via calcium-dependent and calcium-independent mechanisms and suggest that modulation of neuronal sodium channels may play a role in calcium- dependent neuronal plasticity.

Characterization of a voltage-dependent Na(+) current in human esophageal smooth muscle.

The inward currents in human esophageal smooth muscle cells were characterized using patch-clamp electrophysiology and RT-PCR revealed mRNA transcripts for Na(x), the "atypical" Na(+) channel isoform, as well as Na(v)1.4.