# Renal Vascular Smooth Muscle NaV Channels: Regulation and Contribution to Hypoperfusion in Neonatal Ischemic Acute Kidney Injury

> **NIH DK R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2026 · $588,892

## Abstract

Voltage-gated sodium (NaV) channels are essential membrane proteins that mediate sodium ion (Na⁺) influx in
response to membrane depolarization. This rapid Na⁺ entry is critical for generating and propagating action
potentials in excitable cells, including neurons, skeletal muscle, and cardiac muscle. The nine functionally
characterized NaV isoforms (NaV1.1–NaV1.9), encoded by SCN genes, exhibit distinct tissue distributions and
physiological functions. Mutations in NaV channels contribute to a range of neonatal and adult diseases,
highlighting their role in pathological processes. While their contributions to neuronal and cardiac excitability are
well established, NaV channels are also expressed in the vasculature, where their pathophysiological significance
remains unclear. Although NaV channels have been identified in mesenteric, pulmonary, coronary, and femoral
arteries, their regulation and function in the renal preglomerular microvasculature remain unexplored. Our
preliminary findings suggest that NaV1.5 contributes to the regulation of intrarenal arterial tone in the neonatal
kidney, revealing a previously underappreciated role for this channel in neonatal vascular physiology. In neonatal
pig renal vascular smooth muscle cells (VSMCs), NaV1.5 channels are spatially localized in close proximity to
the Na⁺-Ca²⁺ exchanger (NCX). Activation of NaV channels promotes Ca²⁺ influx and vasoconstriction through
reverse-mode NCX activity and L-type Ca²⁺ channels (LTCCs). Additionally, hypoxia/reoxygenation (H/R)
stimulates contraction of the neonatal pig renal artery through the NaV-NCX-LTCC axis. Our pilot studies further
suggest that nitric oxide (NO) regulates NaV1.5 expression in neonatal renal VSMCs via the forkhead box protein
O1 signaling pathway, a mechanism that may drive alterations in endothelial-to-VSMC signal transduction and
contribute to renal ischemia-reperfusion (IR)-induced hypoperfusion—a key factor in the development of acute
kidney injury (AKI). Thi

## Key facts

- **NIH application ID:** 11311445
- **Project number:** 1R01DK146365-01
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Adebowale  Adebiyi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** DK
- **Fiscal year:** 2026
- **Award amount:** $588,892
- **Award type:** 1
- **Project period:** 2026-02-05T00:00:00 → 2029-11-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11311445

## Citation

> US National Institutes of Health, RePORTER application 11311445, Renal Vascular Smooth Muscle NaV Channels: Regulation and Contribution to Hypoperfusion in Neonatal Ischemic Acute Kidney Injury (1R01DK146365-01). Retrieved via AI Analytics 2026-07-03 from https://api.ai-analytics.org/grant/nih/11311445. Licensed CC0.

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