Issues

JGP study shows that disruption of membrane cholesterol alters the organization and activity of mechanosensitive PIEZO1 channels.

Closing the cycle of Kv channel slow inactivation gating.

Kv7 channels are powerfully regulated by a wide variety of physiological and pharmacological signals. Larsson et al. describe the direct modulation of Kv7 channels by endocannabinoids and explore how combinations of Kv7 activators with distinct subtype specificities might lead to effective and selective drug cocktails.

Large changes in energy metabolism are associated with minimal alterations in surface temperature of isolated mammalian cells.

Szanto et al. propose a new gating scheme to explain how the Shaker family of voltage-gated potassium channels are inactivated at negative membrane potentials and how these channels recover from this state.

The anticonvulsant retigabine targets the neuronal M-channel but has adverse clinical effects due to its poor K_V7 subtype specificity. Larsson et al. reveal that the selectivity of retigabine is improved by coapplication with the endocannabinoid arachidonoyl-L-serine.

Living cells convert the hydrolytic energy of ATP to heat during various biochemical reactions. Oyama et al. show that thermogenesis increases temperature on the order of 1°C only proximal to the heat source, but not on a global basis in either non-excitable or excitable cells.

In murine cortical collecting duct cells, prostaglandin E₂ (PGE₂) stimulates transepithelial sodium transport mediated by the epithelial sodium channel (ENaC). PGE₂ is synthesized and secreted by the cells and acts on basolateral prostaglandin E receptor type 4 (EP₄).

The essential mammalian mechanosensitive channel PIEZO1 organizes in the plasma membrane into nanometric clusters that depend on the integrity of cholesterol domains to rapidly detect applied force and especially inactivate synchronously, the most commonly altered feature of PIEZO1 in pathology.