Calmodulin is involved in membrane depolarization-mediated survival of motoneurons by phosphatidylinositol-3 kinase- and MAPK-independent pathways.

In the present work, we find that the elevation of extracellular K+ concentration promotes the survival of chick spinal cord motoneurons in vitro deprived of any neurotrophic support. This treatment induces chronic depolarization of the neuronal plasma membrane, which activates L-type voltage-dependent Ca2+ channels, resulting in Ca2+ influx and elevation of the cytosolic free Ca2+ concentration. Pharmacological reduction of intracellular free Ca2+ or withdrawal of extracellular Ca2+ reversed the effects of depolarization on survival.

Outwardly rectifying Cl- channel in guinea pig small intestinal villus enterocytes: effect of inhibitors.

Previous studies in enterocytes isolated from the villus region of small intestinal epithelium have identified a macroscopic current carried by Cl-. In this work a single-channel patch-clamp study was carried out in the same cells, and a spontaneously active, outwardly rectifying Cl- channel was identified and proposed to underlie the whole cell current. The channel had conductances of 62 and 19 pS at 80 and -80 mV, respectively, in symmetrical Cl- solutions in excised patches.

Sensory receptors in the anterior uvea of the cat's eye. An in vitro study.

Purpose: To identify electrophysiologically the functional types of sensory fibers innervating the iris and the ciliary body of the cat's eye.

Methods: The uveal tract tract of cat's eye was excised and placed in a superfusion chamber. Recordings were made from single afferent units of ciliary nerve branches responding to mechanical stimulation of the iridal surface, the ciliary body, and the choroid with a nylon filament or a glass rod.

Drug efflux mediated by the human multidrug resistance P-glycoprotein is inhibited by cell swelling.

P-glycoprotein (P-gp), the product of the human multidrug resistance (MDR1) gene, confers multidrug resistance on cells by acting as an ATP-dependent drug transporter. A method using confocal microscopy was developed to measure the transport activity of P-gp from the rate of movement of doxorubicin, a fluorescent substrate of P-gp, across the membrane of a single cell. Recent work has shown that expression of P-gp enhances the activation of chloride channels in response to cell swelling, suggesting that membrane stretch might switch P-gp from a drug-transporting mode to a mode in which it activates chloride channels.

Tamoxifen blocks chloride channels. A possible mechanism for cataract formation.

Tamoxifen is an antiestrogen frequently used in the treatment of breast cancer and is currently being assessed as a prophylactic for those at high risk of developing tumors. We have found that tamoxifen and its derivatives are high-affinity blockers of specific chloride channels. This blockade appears to be independent of the interaction of tamoxifen with the estrogen receptor and therefore reflects an alternative cellular target.