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Biomedical subjects

M C Fishman

Publications and source records attributed to M C Fishman.

155 records · Page 9Linked to original sources
PubMed1981

Immobilization of concanavalin A receptors during differentiation of neuroblastoma cells.

Neuroblastoma cells serve as a useful model of neuronal development because compounds such as dimethyl sulphoxide (DMSO) and dibutyryl cyclic AMP cause them to undergo a process of controlled differentiation in tissue culture, during which they can extend long processes, develop characteristic excitability mechanisms, synthesize neurotransmitters and form synapses. We have used the technique of fluorescence photobleaching recovery to study the lateral mobility of cell-surface constituents during the differentiation of neuroblastoma clone N1E-115 cells. The concanavalin A (Con A) binding sites appear as discrete patches distributed over the entire cell surface and exhibit lateral mobility in undifferentiated cells comparable with that of surface glycoproteins of other cells. After induction of differentiation, however, the vast majority of Con A binding sites become immobilized, and we present data which suggest that the mechanism of this immobilization may involve linkage to the internal actin network.

Actins↗
PubMed1981

Potassium current suppression by quinidine reveals additional calcium currents in neuroblastoma cells.

Quinine and quinidine have been evaluated with regard to their effects on the electrical activity of neuroblastoma cells. Under voltage-clamp conditions, we have found that quinine and quinidine block both the voltage-dependent and Ca2+-dependent K+ conductances. Blockage of the voltage-dependent K+ channel is manifest as an increase in the amplitude and in the duration of the action potential. Blockage of the Ca2+-dependent K+ channel in Na+-free (replaced by Tris) solutions containing 6.8 mM Ca2+ and tetraethylammonium ion or 4-aminopyridine (to block the voltage-dependent K+ current) is seen as a further prolongation of the Ca2+ action potential and diminution of the after-hyperpolarization. A critical role of the Ca2+-dependent K+ conductance in modulation of the rate and duration of trains of Ca2+ action potentials is shown by the use of low concentrations (5-40 microM) of quinine or quinidine, which diminish the Ca2+-dependent K+ conductance in a graded manner. After complete blockade of K+ currents, the peak Ca2+ currents are enhanced at all voltages, especially at values more positive than -30 mV, where a steady-state inward current appears as well. In this same voltage range, the decay of the Ca2+ current exhibits two time constants--that of the transient inward current, which is about 20 msec, and a much slower (approximately 2000 msec) component. It is suggested that neuroblastoma cells have two types of calcium channels--one which generates the Ca2+ action potential and a second, distinguished by activation at more depolarized levels and by a slow rate of inactivation, which underlies the calcium entry necessary to activate the Ca2+-dependent K+ conductance.

Action Potentials↗
PubMed1981

Depolarization-induced synaptic plasticity at cholinergic synapses in tissue culture.

Many synaptic connections are rejected during development, and the remainder are stabilized. Whether neuronal activity is important in this remodeling remains unknown. Cholinergic synapses are formed in tissue culture between the hybrid NG108-15 (neuroblastoma X glioma) cell and skeletal myotubes. We have investigated changes in these synapses brought about by chronic depolarization. Most myotubes are innervated under control conditions and recording from a myotube while stimulating a neighboring hybrid cell demonstrates that most hybrid-myotube pairs in anatomical proximity also are connected synaptically. Multiple innervation of one myotube by several hybrid cells is common. After 24 to 72 hr of cell depolarization with low concentrations of veratridine, myotubes continue to evidence synaptic activity, but the chance of evoking activity, in a given myotube by stimulation of a neighboring hybrid cell, is diminished to 30% of control values; only 5% of myotubes can be demonstrated to still have multiple innervation. However, the efficacy of synapses that persists after veratridine exposure is comparable to control. By 24 hr after removal of veratridine, synapse number returns to control levels. Tetrodotoxin prevents these effects. We suggest that components responsible for the well known development change from polyneuronal to mononeuronal innervation may be present and accessible to manipulation in this relatively well defined tissue culture system.

Acetylcholine↗
PubMed1979

Ionophore A23187 disrupts membrane structure by modifying protein-lipid interactions.

The physiological function of membrane-boudn protein clearly depends on the nature of its neighbouring lipid. However, the question of how critical the protein is to the structure and function of membrane lipid has received much less attention. There is some evidence that lipid surrounding membrane protein, 'boundary lipid', may be more ordered than continuum lipid. Protein can also alter the enthalpy and temperature of pure lipid-phase transitions. However, controversy surrounds the question of whether membrane proteins determine long-range aspects of lipid structure or merly perturb their local environments. Here, we demonstrate that a lipophilic substance, the calcium ionophore, A23187 (Lilly), dramatically disorders the lipid structure of the membrane and that this phenomenon depends on the presence of proteins.

Animals↗
PubMed1979

Endogenous digitalis-like activity in mammalian brain.

A fraction of brain has been prepared that contains a substance mimicking actions of the digitalis glycosides. It both blocks the binding of [3H]ouabain to Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and inhibits the uptake of 86Rb+ into human erythrocytes. Partial isolation was achieved by Sephadex G-10 fractionation and subsequent desalting. This activity is potentially capable of regulating ionic fluxes and concentration gradients across the cell membrane.

Animals↗
PubMed1976

Effects of hypoxia, heat, and humidity on physical performance.

The effects of hot, humid environment were compared with the effects of high altitude on the physical performance capacity of Ne-palese residents by measuring oxygen uptakes and heart rates at various work rates. The following groups of men were selected: 66 residents of a hot and humid environment in the Terai at sea level; 24 residents and 16 sojourners at 3,8000 m. The maximal oxygen uptake of the sea-level residents was, on the average, 2.55 1.min-1, at which a maximal heart rate of about 200 beats/min was reached. The sojourners at 3,800 m showed a higher maximal oxygen uptake (2.94 1. min-1) at their maximal heart rate of about 175 beats/min. The residents of 3,800 m achieved a similiar oxygen uptake as the sojourners, but did not show a similar maximal heart rate limitation, suggesting that they were capable of achieving a higher maximal oxygen uptake. This study shows that hot, humid environment at sea level is as much incapacitating as is hypoxia at high altitude.

Adult↗