1. Recordings were made from single nerve fibers in barbiturate-anesthetized cats in the midline trapezoid body, a location that permits selective sampling of efferent cells of the ventral cochlear nucleus. Single units were localized to either the dorsal or ventral components of the trapezoid body. The fibers were physiologically classified on the basis of their peristimulus time histograms (PSTH) and receptive-field properties. In addition, low characteristic frequency (CF) units were probed for rapid rate and phase shifts with increases in intensity. The projection patterns of some fibers were traced by iontophoresing horseradish peroxidase (HRP) into their axons. 2. HRP-labeled fibers most likely originated from globular bushy cells of the ventral cochlear nucleus in that they sent a large branch into the contralateral medial nucleus of the trapezoid body which terminated in a calyceal ending and an ipsilateral branch into the lateral nucleus of the trapezoid body. A thin branch, usually starting from the large branch, wound its way through the medial nucleus of the trapezoid body to its termination in the ventral nucleus of the trapezoid body. Additional branches from the parent axon could pass through medial periolivary groups throughout the rostrocaudal extent of the superior olivary complex. The parent fiber was traced as far as the ventral lateral lemniscus where it faded before reaching its termination. 3. The majority of units were recorded in the ventral component of the trapezoid body. Although the ventral component is comprised of both large and small diameter fibers, our sample was biased to the larger diameter fibers representing the activity of axons originating from globular bushy cells in the ventral cochlear nucleus. Ventral component units were not tonotopically arrayed and had CFs that spanned the audible range for cats. HRP labeling of ventral component axons revealed that the section of the axon traveling through the midline shifted its dorsal-ventral location. This pattern was compatible with the lack of tonotopy found in the ventral component. Recordings were also made from the dorsal component of the trapezoid body, which contained medium diameter axons. These axons originated from spherical bushy cells in the ventral cochlear nucleus. Dorsal component units were tonotopically arrayed and had CFs less than 7 kHz. 4. Cells were characterized by their PSTH at CF. Primary-like and phase-locked units constituted most of the dorsal component units.(ABSTRACT TRUNCATED AT 400 WORDS)

Systemic lupus erythematosus (SLE) is an autoimmune/inflammatory disease characterized by autoantibody production and abnormal T cells that infiltrate tissues through not well-known mechanisms. We report that SLE T lymphocytes display increased levels of CD44, ezrin, radixin, and moesin (ERM) phosphorylation, stronger actin polymerization, higher polar cap formation, and enhanced adhesion and chemotactic migration compared with T cells from patients with rheumatoid arthritis and normal individuals. Silencing of CD44 by CD44 small interfering RNA in SLE T cells inhibited significantly their ability to adhere and migrate as did treatment with Rho kinase and actin polymerization inhibitors. Forced expression of T567D-ezrin, a phosphorylation-mimic form, enhanced remarkably the adhesion and migration rate of normal T cells. Anti-CD3/TCR autoantibodies present in SLE sera caused increased ERM phosphorylation, adhesion, and migration in normal T cells. pERM and CD44 are highly expressed in T cells infiltrating in the kidneys of patients with lupus nephritis. These data prove that increased ERM phosphorylation represents a key molecular abnormality that guides T cell adhesion and migration in SLE patients.

Inward barium current (IBa) through voltage-gated calcium channels was recorded from chick cochlear hair cells using the whole-cell clamp technique. IBa was sensitive to dihydropyridines and insensitive to the peptide toxins omega-agatoxin IVa, omega-conotoxin GVIa, and omega-conotoxin MVIIC. Changing the holding potential over a -40 to -80 mV range had no effect on the time course or magnitude of IBa nor did it reveal any inactivating inward currents. The activation of IBa was modeled with Hodgkin-Huxley m2 kinetics. The time constant of activation, tau m, was 550 microseconds at -30 mV and gradually decreased to 100 microseconds at +50 mV. A Boltzmann fit to the activation curve, m infinity, yielded a half activation voltage of -15 mV and a steepness factor of 7.8 mV. Opening and closing rate constants, alpha m and beta m, were calculated from tau m and m infinity, then fit with modified exponential functions. The H-H model derived by evaluating the exponential functions for alpha m and beta m not only provided an excellent fit to the time course of IBa activation, but was predictive of the time course and magnitude of the IBa tail current. No differences in kinetics or voltage dependence of activation of IBa were found between tall and short hair cells. We conclude that both tall and short hair cells of the chick cochlea predominantly, if not exclusively, express noninactivating L-type calcium channels. These channels are therefore responsible for processes requiring voltage-dependent calcium entry through the basolateral cell membrane, such as transmitter release and activation of Ca(2+)-dependent K+ channels.

Field potentials were recorded along radial tracks in scala tympani and scala vestibuli of the guinea-pig cochlea. A current density analysis revealed standing current density profiles that were qualitatively similar between animals and between the second and third cochlear turns. Radial standing current densities were greatest at or near the spiral ligament. All the scala vestibuli current density profiles were scaled versions of one another while the scala tympani current density profiles showed more variability. Acoustic stimuli modulated the standing current and there was a cochlear microphonic current density peak in scala tympani near the organ of Corti. The results are summarized with a current-density field line model, the key element of which is a constant current pumped into scale media by the stria vascularis. The standing potential gradients drive current from each perilymphatic chamber into the spiral ligament en route to the lateral surface of the stria vascularis. The strial current is divided between the receptor cell pathway and leakage pathways. The standing current through the leakage pathways is indirectly modulated by acoustic stimulation through the modulation of the endocochlear potential. The reciprocal modulation of current between hair cell and leakage pathways suggests that the stria vascularis maintains a constant current during acoustic stimulation. The cochlear standing current is similar to the retinal dark current in its importance for sensory transduction but the fact that the silent current is generated by the stria vascularis and not the receptor cells provides significant benefits for the detection of mechanical stimuli.

SUMMARYLarge conductance, calcium-activated (BK) potassium channels play a central role in the excitability of cochlear hair cells. In mammalian brains, one class of these channels, termed Slo, is encoded by homologues of the Drosophila ' slo poke ' gene. By homology screening with mouse Slo cDNA, we have isolated a fulllength clone (cSlo1) from a chick's cochlear cDNA library. cSlo1 had greater than 90 % identity with mouse Slo at the amino acid level, and was even better matched to a human brain Slo at the amino and carboxy termini. cSlo1 had none of the additional exons found in splice variants from mammalian brain. The reverse transcriptase polymerase chain reaction (RT-PCR) was used to show expression of cSlo1 in the microdissected hair cell epithelium (basilar papilla). Transient transfection of HEK 293 cells demonstrated that cSlo1 encoded a potassium channel whose conductance averaged 224 pS at j60 mV in symmetrical 140 mM K + . Macroscopic currents through cSlo1 channels were blocked by scorpion toxin or tetraethyl ammonium, and were voltage and calcium dependent. cSlo1 is likely to encode BK-type calcium-activated potassium channels in cochlear hair cells.