The present study was undertaken to determine whether or not physical contact with the substratum is essential for the stimulatory effect of extracellular matrix (ECM) on corneal epithelial collagen synthesis. Previous studies showed that collagenous substrata stimulate isolated epithelia to produce three times as much collagen as they produce on noncollagenous substrate; killed collagenous sub...

The present study was designed to test the hypothesis that addition of anticaspase cocktails (inhibiting caspases and thus blocking apoptosis) to the extenders increases the post-thaw viability of equine spermatozoa. The addition of caspase inhibitors failed to improve the acrosome and plasma membrane integrity of spermatozoa, suggesting that in equine sperm cryopreservation protocols, the addi...

The mechanism of Cl ion permeation through single cystic fibrosis transmembrane conductance regulator (CFTR) channels was studied using the channel-blocking ion gluconate. High concentrations of intracellular gluconate ions cause a rapid, voltage-dependent block of CFTR Cl channels by binding to a site approximately 40% of the way through the transmembrane electric field. The affinity of glucon...

Inwardly rectifying K+ channels conduct more inward than outward current as a result of voltage-dependent block of the channel pore by intracellular Mg2+ and polyamines. We investigated the molecular mechanism and structural determinants of inward rectification and ion permeation in a strongly rectifying channel, IRK1. Block by Mg2+ and polyamines is found not to conform to one-to-one binding, ...

The Erwinia ligand-gated ion channel (ELIC) is a bacterial homologue of eukaryotic Cys-loop ligand-gated ion channels. This protein has the potential to be a useful model for Cys-loop receptors but is unusual in that it has an aromatic residue (Phe) facing into the pore, leading to some predictions that this protein is incapable of ion flux. Subsequent studies have shown this is not the case, s...

If you ask most medical school deans if they have a course, program, or center doing bioethics, they will enthusiastically assure you that they do. And their enthusiasm for bioethics grows exponentially in proportion to their interest in showing that they are doing something about managing research ethics issues at their institutions. The same can be said about the entire biomedical research es...

When attached to specific sites near the S4 segment of the nonconducting (W434F) Shaker potassium channel, the fluorescent probe tetramethylrhodamine maleimide undergoes voltage-dependent changes in intensity that correlate with the movement of the voltage sensor (Mannuzzu, L.M., M.M. Moronne, and E.Y. Isacoff. 1996. Science. 271:213-216; Cha, A., and F. Bezanilla. 1997. Neuron. 19:1127-1140). ...

Synaptic mechanisms of plasticity are calcium-dependent processes that are affected by dysfunction of mitochondrial calcium buffering. Recently, we observed that mice deficient in mitochondrial voltage-dependent anion channels, the outer component of the mitochondrial permeability transition pore, have impairments in learning and hippocampal synaptic plasticity, suggesting that the mitochondria...

One major determinant of the efficacy of antibiotics on gram-negative bacteria is the passage through the outer membrane. During transport of the fluoroquinolone enrofloxacin through the trimeric outer membrane protein OmpF of Escherichia coli, the antibiotic interacts with two binding sites within the pore, thus partially blocking the ionic current. The modulation of one affinity site by Mg(2+...

ClC chloride channels are voltage-gated transmembrane proteins that have been associated with a wide range of regulatory roles in vertebrates. To accomplish their function, they allow small inorganic anions to efficiently pass through, while blocking the passage of all other particles. Understanding the conduction mechanism of ClC has been the subject of many experimental investigations, but un...