Volume regulation of murine T lymphocytes relies on voltage-dependent and two-pore domain potassium channels

A variety of ion channels are supposed to orchestrate the homoeostatic volume regulation in T lymphocytes. However, the relative contribution of different potassium channels to the osmotic volume regulation and in particular to the regulatory volume decrease (RVD) in T cells is far from clear. This study explores a putative role of the newly identified K2P channels (TASK1, TASK2, TASK3 and TRESK) along with the voltage-gated potassium channel KV1.3 and the calcium-activated potassium channel KCa3.1 in the RVD of murine T lymphocytes, using genetic and pharmacological approaches. K2P channel knockouts exerted profound effects on the osmotic properties of murine T lymphocytes, as revealed by reduced water and RVD-related solute permeabilities. Moreover, both genetic and pharmacological data proved a key role of KV1.3 and TASK2 channels in the RVD of murine T cells exposed to hypotonic saline. Our experiments demonstrate a leading role of potassium channels in the osmoregulation of T lymphocytes under different conditions. In summary, the present study sheds new light on the complex and partially redundant network of potassium channels involved in the basic physiological process of the cellular volume homeostasis and extends the repertoire of potassium channels by the family of K2P channels.

Research highlights
► Investigation of the functional role of members of the K2P family in volume regulation in lymphocytes
► KV1.3 and TASK2 are mainly responsible for RVD in murine T lymphocytes
► The impact of K2P channels on RVD has been shown to depend on the cell activation status