Paranodin, a glycoprotein of neuronal paranodal membranes.

Ranvier nodes are flanked by paranodal regions, at the level of which oligodendrocytes or Schwann cells interact closely with axons. Paranodes play a critical role in the physiological properties of myelinated nerve fibers. Paranodin, a prominent 180 kDa transmembrane neuronal glycoprotein, was purified and cloned from adult rat brain, and found to be highly concentrated in axonal membranes at their junction with myelinating glial cells, in paranodes of central and peripheral nerve fibers. The large extracellular domain of paranodin is related to neurexins, and its short intracellular tail binds protein 4.1, a cytoskeleton-anchoring protein. Paranodin may be a critical component of the macromolecular complex involved in the tight interactions between axons and myelinating glial cells characteristic of the paranodal region.

Modulation of the cardiac transient outward current by catecholamines.

We studied modulation of the transient outward current in single canine Purkinje cells that were voltage clamped under Ca2+-free conditions using the patch pipette. The current showed two exponential time constants of inactivation (48, 352 ms at +58 mV and 53, 325 ms at +78 mV). Norepinephrine or isoproterenol modified the inactivation kinetics of this current without affecting the activation kinetics. The half maximum dose for norepinephrine effect was 1.9 x 10(-8) M and the effect was saturated at 10(-6) M. Norepinephrine or isoproterenol reduced the amplitude of the fast time constant component of inactivation, while increasing the amplitude of the slow component, without changing their time constants. They also increased the amplitude of a time-independent current component. The beta-antagonist, sotalol, blocked the norepinephrine effect on the transient outward current. On the other hand, both activation of adenyl cyclase by forskolin and increase of intracellular cAMP concentration produced the same effect as exposure to norepinephrine. Intracellular perfusion with the catalytic subunit of the cAMP-activated protein kinase reproduced the modulation of the current. These results suggest a role for neurotransmitter regulation of the transient outward current in cardiac cells, perhaps by channel phosphorylation.

Effects of rate of air pressure change on tympanometry.

The effects of two rates of air pressure change upon the pressure and compliance values and classification of tympanograms were determined in normal subjects and subjects with middle ear pathology. Significant differences in the magnitude of compliance and the air pressure corresponding to maximum compliance were observed. The more rapid rate was associated with a higher measured compliance in both groups of ears. In normal ears, the faster pressure change resulted in a shift in the point of maximum compliance toward a more negative pressure, while the reverse was true for ears with middle ear disease. The different rates of pressure change resulted in a different classification of the associated tympanograms for approximately 25% of the impaired ears. These findings imply that the interpretation of the relative normalcy of the tympanogram should take into account the rate of air pressure change used to acquire the result.

Induction of differentiation in mouse neuroblastoma cells.

In the presence of 1--2% dimethyl sulfoxide (DMSO), mouse neuroblastoma cells are induced to differentiate morphologically as well as electrically. In addition, treatment of neurolbastoma cells with 2% DMSO results in a marked increase in the veratridine-activated K+ or Rb+ efflux. At 4% DMSO, neurite outgrowth is completely repressed and electrical activity is poorly developed. However, at this concentration, the cells have a relatively high resting potential which suggested that membrane components determining passive and active permeability properties are not necessarily under coordinated control. Induction of differentiation by 2% DMSO is also accompanied by an increase in a heavier molecular form of acetylcholinesterase sedimenting at 10.5S. The effect of other agents on the growth and differentiation of neuroblastoma cells is also presented.

Maturation of neuroblastoma cells in the presence of dimethylsulfoxide.

Addition of dimethylsulfoxide at concentrations of 1% and 2% (vol/vol) to cells of mouse neuroblastoma clone NIE-115 in the confluent phase of growth resulted in the production of morphologically differentiated cultures with extensive process formation. Cell maintained in 2% dimethylsulfoxide remained in a stable nondividing condition for periods of up to 4 weeks. A high degree of electrical excitability was found in these cells, but there was no clear correlation of this property with the level of induction of either acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7) or tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2]. In addition, intracellular levels of cyclic 3':5'-AMP were not elevated in fully morphologically and electrically differentiated cells. While cell division was markedly inhibited by 2% or higher concentrations of dimethylsulfoxide, at 1% growth continued at a somewhat slowed rate and such cultures exhibited enhanced process formation and electrical activity for a relatively short period. High concentrations (3% or 4%) of dimethylsulfoxide totally suppressed process formation and did not result in increased excitability, but cells maintained high resting potentials. The results suggest that the development of the excitable membrane in neuroblastoma cells may be expressed independently of neurospecific enzyme induction, and does not require a sustained elevation of cyclic 3':5'-AMP levels.

Enhancement of the electrical excitability of neuroblastoma cells by valinomycin.

Mouse neuroblastoma cells in stationary phase of growth display partially developed electrical properties. Addition of the K+ selective carrier valinomycin to these cells causes rapid enhancement of electrical excitability. We suggest that the appearance of molecules with properties similar to valinomycin is essential for the full expression of electrical excitability in differentiating neuroblastoma.