Biomedical subjects

B L Kagan

Publications and source records attributed to B L Kagan.

40 records · Page 3Linked to original sources

PubMed1981

Mode of action of colicin ib: formation of ion-permeable membrane channels.

Addition of purified colicin Ib to whole Escherichia coli cells or cytoplasmic membrane vesicles inhibits their subsequent ability to generate a membrane potential. In addition, this colicin is shown to bring about a voltage-dependent increase in the conductance of an artificial planar bilayer membrane prepared from soybean phospholipids. This results from the formation of ion-permeable channels. These data provide strong evidence that the depolarization of Escherichia coli cells by this colicin results from an Ib-induced increase in membrane permeability to ions.

Cell Membrane↗

PubMed1981

Diphtheria toxin fragment forms large pores in phospholipid bilayer membranes.

The cytotoxic effect of diphtheria toxin requires the entry of its enzymatic A fragment (Mr approximately 21,000) into the cytosol of sensitive cells. We show that the B45 fragment (Mr approximately 24,000) forms, in lipid bilayers, pores that are large enough (diameter greater than or equal to 18 A) to allow the passage of extended fragment A. Pore formation is maximal when the B45-containing side is at low pH (4.7) and the opposite side is at high pH (7.4). These conditions resemble the pH gradient existing across lysosomal membranes. We suggest that fragment A passes through these pores from acidic endocytotic vesicles (lysosomes?) to the cytosol.

Conductometry↗

PubMed1978

Colicin K acts by forming voltage-dependent channels in phospholipid bilayer membranes.

The bactericidal action of colicins K, E1, Ia, and other functionally related colicins involves disruption of active transport and leakage of ions from the cell. We show that a single colicin K molecule can form a voltage-dependent, relatively nonselective, ion-permeable channel of a few picosiemens conductance in a planar phospholipid bilayer membrane. In a membrane containing many of these channels, the ratio of the number of conducting to nonconducting channels changes e-fold per 3.7 mV. We suggest that the physiological effects of colicin K and functionally related colicins result from their ability to form ion-permeable channels in the bacterial plasma membrane.

Biological Transport, Active↗

PubMedDate not supplied

The channel hypothesis of Huntington's disease.

Extended tracts of polyglutamine (PG) have been implicated in the pathogenicity of the mutant protein huntingtin and have been shown to form ion channels in planar lipid bilayers. These lines of evidence suggest that huntingtin and other PG mutant proteins may damage cells via a channel mechanism. This mechanism could cause damage to the plasma membrane by running down ionic gradients, discharging membrane potential; or allowing influx of toxic ions such as Ca(2+). PG damage to intracellular membranes such as the lysosomal membrane or the mitochondrial membrane could also injure cells via leakage of toxic enzymes or triggering of apoptosis. The channel mechanism is well-established for microbial toxins, and the existence of at least six other "amyloid" channels relevant to diseases such as Alzheimer's and Creutzfeld-Jakob, suggests that this may be a widespread pathogenic mechanism.

Humans↗