Animal Physiology - Cell

At the heart of animal function lies the physiology of individual cells, where dynamic membranes, organelles and molecular circuits translate external cues into organised responses. Ion channels and pumps generate and maintain electrochemical gradients that underpin nerve impulses, muscle contraction and electrolyte balance. Water channels and solute carriers regulate volume and nutrient flux, preserving homeostasis under osmotic stress. Intracellular signalling networks—driven by phosphorylation cascades, second messengers and transcription factors—integrate hormonal, mechanical and metabolic inputs to control secretion, growth and differentiation. Mitochondria and specialised buffer proteins orchestrate calcium handling and ATP production, fine-tuning energy supply and signal transduction. Quality-control pathways such as autophagy and the ubiquitin–proteasome system ensure proteome integrity during stress or nutrient deprivation. Recent innovations in structural biology, genome engineering and high-resolution imaging are illuminating these mechanisms across diverse cell types, deepening our understanding of development, adaptation and disease. A cellular perspective thus underpins advances in pharmacology, regenerative medicine and environmental management, reflecting the central role of single-cell physiology in animal biology.

Research from Nature Portfolio

Structural and computational studies of large-conductance calcium-activated potassium (BK) channels have overturned the classical view of gating. Instead of a physical constriction, subtle shifts in pore-lining hydrophobic residues induce dewetting transitions that erect a thermodynamic barrier to K⁺ flow in the closed state. This hydrophobic gating mechanism reframes how excitability is controlled in smooth muscle and neuronal cells and suggests novel targets for selective modulators.

In cardiac myocytes, phosphorylation of the sarco/endoplasmic reticulum Ca²⁺-ATPase isoform 2 (SERCA2) at serine 663 has been identified as a pathological switch during ischaemia–reperfusion injury. Elevated modification at this site reduces pump efficiency, promotes cytosolic calcium overload and enlarges infarct areas. Preventing serine 663 phosphorylation restores calcium reuptake, enhances cell survival and limits myocardial damage, opening new avenues for cardioprotective therapies.

Research from all publishers

Insights into renal water handling have emerged from studies disrupting mitochondrial electron transport in collecting-duct principal cells. Impairment of complex III triggers activation of AMP-activated protein kinase (AMPK), leading to reduced aquaporin-2 (AQP2) abundance and compromised urinary concentration. Pharmacological inhibition of AMPK reverses AQP2 downregulation, directly linking cellular energy status to water channel homeostasis.

Tamoxifen, a selective oestrogen receptor modulator, has been shown to counteract downregulation of basolateral aquaporin-3 (AQP3) in models of obstructive nephropathy and lithium-induced nephrogenic diabetes insipidus. Treatment preserves AQP3 expression and alters membrane protein localisation, suggesting that hormone-receptor pathways can be harnessed to stabilise epithelial water permeability in renal disorders.

Cryo-electron microscopy of the human secretory-pathway Ca²⁺-ATPase (SPCA1) has captured six distinct intermediate conformations. These structures reveal unique rearrangements of transmembrane helices during ATP binding and phosphorylation cycles, delineating a transport mechanism specific to Golgi calcium homeostasis and informing the design of targeted modulators for secretory-pathway dysfunctions.

Animal Physiology - Cell publication trend

The graph below shows the total number of articles in animal physiology - cell across all publications each year (not limited to Nature Index journals).

Technical terms

Ion channel: Transmembrane protein that permits selective ion flow along electrochemical gradients.

Hydrophobic gating: Regulation of ion permeation by changes in pore-lining hydrophobicity that alter water occupancy and create an energetic barrier.

SERCA2: Sarco/endoplasmic reticulum Ca²⁺-ATPase isoform critical for pumping calcium into the SR to promote muscle relaxation.

Aquaporin (AQP): Membrane channel protein family enabling rapid and selective water transport.

AMP-activated protein kinase (AMPK): Cellular energy sensor that modulates metabolism in response to changes in AMP/ATP ratio.

Cryo-electron microscopy: Imaging technique that captures macromolecular structures at cryogenic temperatures to resolve distinct functional states.

References

1. Hydrophobic gating in BK channels. Nature Communications (2018).
2. SERCA2 phosphorylation at serine 663 is a key regulator of Ca2+ homeostasis in heart diseases. Nature Communications (2023).
3. Disruption of mitochondrial electron transport impairs urinary concentration via AMPK-dependent suppression of aquaporin-2. JCI Insight (2024).
4. Tamoxifen Affects Aquaporin-3 Expression and Subcellular Localization in Rat and Human Renal Collecting Ducts. Cells (2023).
5. Structure and transport mechanism of the human calcium pump SPCA1. Cell Research (2023).