Source Data for paper "Membrane Lipid Nanodomains Modulate HCN Pacemaker Channels in Nociceptor DRG Neurons"

Lipid domains, particularly detergent-resistant, ordered membrane domains (OMDs), form specialized compartments within cell membranes that play critical roles in cell signaling. OMDs, rich in cholesterol and sphingolipids, vary in size and are dynamic, adapting to physiological changes. Techniques like super-resolution microscopy and cryo-electron tomography have revealed their structure, though much remains unknown.Lipid domains are implicated in various biological processes, including Alzheimer's disease, viral infections, inflammation, and neuropathic pain. Notably, in models of chemotherapy-induced neuropathy and arthritis, targeting these domains has alleviated symptoms, suggesting potential for therapeutic interventions.Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, particularly HCN2, regulate neuronal excitability and are linked to chronic pain. These channels localize within OMDs, and their function is modulated by lipid domain composition. Disruption of OMDs in nociceptor neurons enhances action potential firing and is associated with increased HCN channel activity, contributing to neuropathic pain. The study highlights the importance of lipid domains in modulating HCN channels, suggesting that their disruption may be a key mechanism in neuropathic pain development.