Journal articles

$\textbf{Background}$ Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The K$_V$7 family (K$_V$7.1-K$_V$7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways.

The African naked mole-rat’s ($\textit{Heterocephalus glaber}$) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain.

Although increasingly popular as a laboratory species, very little is known about the peripheral auditory system of the naked mole-rat, $\textit{Heterocephalus glaber}$. In this study, middle and inner ears of naked mole-rats of a range of ages were examined using micro-computed tomography and dissection. The ears of five other bathyergid species ($\textit{Bathyergus suillus}$, $\textit{Cryptomys hottentotus}$, $\textit{Fukomys micklemi}$, $\textit{Georychus capensis}$ and $\textit{Heliophobius argenteocinereus}$) were examined for comparative purposes.

The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function.

Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment.

The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1.

BACKGROUND: A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability.

The naked mole-rat (NMR) is a subterranean rodent that has gained significant attention from the biomedical research community in recent years as molecular mechanisms underlying its unusual biology start to be unraveled. With very low external mortality, NMRs have an unusually long lifespan while showing no signs of aging, such as neurodegeneration or cancer. Furthermore, living underground in large colonies (100 to 300 animals), results in comparatively high carbon dioxide and low oxygen levels, from which NMRs have evolved extreme resistance to both hypoxia and hypercapnia.

Abstract ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a.

ASIC and ENaC are co-expressed in various cell types, and there is evidence for a close association between them. Here, we used atomic force microscopy (AFM) to determine whether ASIC1a and ENaC subunits are able to form cross-clade hybrid ion channels. ASIC1a and ENaC could be co-isolated from detergent extracts of tsA 201 cells co-expressing the two subunits. Isolated proteins were incubated with antibodies against ENaC and Fab fragments against ASIC1a.