Abstract
Anion channels play a stabilizing role in excitability in muscle and neuronal cells and a Cl− transporting role in epithelial cells. Recent investigations have revealed their more general functions including cell volume regulation and cell proliferation. Here, we present additional roles that have been found in our laboratory. First, the volume-sensitive outwardly rectifying (VSOR) Cl− channel, which is ordinary activated by cell swelling, plays an inductive role of apoptotic cell death. An apoptotic inducer rapidly activated the VSOR current without cell swelling and thereby induced apoptotic volume decrease (AVD) in epithelial and cardiac cells. Second, the same channel is involved in excitotoxic neuronal cell death. Stimulation with NMDA induced activation of the VSOR Cl− channel, varicosity formation, somatic swelling and eventually necrotic death in cortical neurons. Third, the maxi-anion channel with a single-channel conductance of around 400 pS serves as the release pathway of ATP, which is an extracellular signal for cell-to-cell communication, in mammary cells, kidney macula densa cells, cardiomyocytes and astrocytes activated by a variety of stimuli. Forth, the maxi-anion channel also mediates glutamate release from cortical astrocytes under ischemic conditions. Molecular understanding of physiological or pathoplysiogical functions of these anion channels will progress after identification of their molecules. [J Physiol Sci. 2006;56 Suppl:S36]