[Effects of the aldose reductase inhibitor on diabetic polyneuropathy--the efficacy of F wave measurement].

The effects of the aldose reductase inhibitor epalrestat (150 mg/day) on electrophysiological function were examined in 22 NIDDM patients with diabetic polyneuropathy for 6 months. Although no significant differences were observed in sensory (the sural nerve) or motor (the posterior tibial nerve) conduction velocities and amplitude, only F wave conduction velocities were significantly improved at 3 and 6 months after the treatment. There were no significant changes in CV-RR, vibration threshold and laboratory data. No serious side effects were observed during the therapeutic trial. This study suggests F wave is appropriate for the assessment of diabetic neuropathy and for therapeutic trials.

A case of primary and generalized allergy to human insulin with no history of any prior insulin exposure.

A generalized hypersensitivity reaction against human insulin was demonstrated in a non-insulin dependent diabetic man treated with only human insulin. The patient had no history of previous insulin exposure or atopy. Because of negative reactions to intracutaneous tests of constituents of the formulation and the presence of insulin-specific IgE antibody, this generalized allergic reaction seems to have been caused by the human insulin itself. Although desensitization was not effective, this allergic reaction was improved both by the treatment with oral antihistamines and desensitization. Cases of generalized and primary allergy against human insulin have been rarely reported making this a very rare case.

A heterogeneous electrophysiological profile of bone marrow-derived mast cells.

Electrophysiological properties of mouse bone marrow-derived mast cells (BMMC) were studied under the whole-cell clamp configuration. About one third of the cells were quiescent, but others expressed either inward or outward currents. Inwardly rectifying (IR) currents were predominant in 14% of the cells, and outwardly rectifying (OR) currents in 24%. The rest (22%) of the cells exhibited both inward and outward currents. The IR currents were eliminated by 1 mM Ba2+, and were partially inhibited by 100 microM quinidine. The reversal potential was dependent on extracellular K+, thereby indicating that K+ mediated the IR currents. The negative conductance region was seen at potentials positive to EK. The OR currents did not apparently depend on the extracellular K+ concentration, but were reduced by lowering the extracellular Cl- concentration. The OR currents were partially blocked by 1 mM Ba2+, and were further blocked by a Cl- channel blocker, 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS). In addition, the reversal potential of the OR currents was positively shifted by decreasing the ratio of external and internal Cl- concentrations, suggesting that Cl- was a major ion carrier. In cells exhibiting IR currents, the membrane potential varied among cells and tended to depolarize by elevating the external K+ concentration. In cells with OR currents, the resting potential was hyperpolarized in association with an increase in conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium-dependent inactivation of inwardly rectifying K+ channel in a tumor mast cell line.

Antigenic stimulation of rat basophilic leukemia (RBL-2H3) cells, a tumor mast cell line, is associated with an increase in intracellular free Ca2+ concentrations ([Ca2+]i) and membrane polarization. We recorded whole cell and single-channel currents through the inwardly rectifying K+ channel, a major resting conductance of cells, using the patch-clamp technique, and we examined interactions between channel activity and [Ca2+]i. With 10 microM Ca2+ in the pipette, the amplitude of whole cell currents gradually declined within 5 min to 48 +/- 13% of that immediately after rupture of the patch membrane, in the presence of 1 mM ATP which minimized intrinsic rundown. In inside-out patches, activity of the channel was reduced by increasing the concentration of Ca2+ in the internal medium, both in the presence and absence of 1 mM ATP, with no apparent change in single-channel conductance. Time-averaged mean current activity in inside-out patches in the presence of 5 microM Ca2+ was less than 50% of that with Ca2+ of 100 nM or less. These results suggest that a rise in [Ca2+]i leads to a closure of the inwardly rectifying K+ channel. In some inside-out patches, inward currents characterized by burst composed of rapid transitions between open and closed states were observed (flickering currents). Single-channel properties of the flickering currents are similar to the inwardly rectifying K+ channel except for kinetics (single-channel conductance of 24.5 +/- 7.9 pS, inward rectification, and permeability to K+).(ABSTRACT TRUNCATED AT 250 WORDS)

Generator potentials and spike initiation in auditory fibers of goldfish.

Responses were recorded extra- or intracellularly from single, small afferent fibers of the goldfish saccule, that is, S2 fibers, to clarify how the spontaneous and sound-evoked firings in these fibers are initiated from generator potentials. Spontaneously active units randomly selected from the saccular nerve of five goldfish (total 78 units) were classified by the coefficient of variation (CV) of interspike intervals into irregular (59 units; CV greater than 0.3), intermediate (10 units), and regular types (9 units; CV less than 0.23). The irregular type showed a burst (38 units) or random (21 units) pattern of firing in spontaneous activity. In cases where a clear generator potential could be recorded in response to each sound wave, spontaneous generator potentials could also be observed in the absence of stimulus sound. These spontaneous potentials were irregular in amplitude and time course, and often contained components much slower than the sound-evoked generator potentials. The sound-evoked generator potentials in S2 fibers were produced with a delay of 0.4-0.85 ms following each sound wave, and had a time course comparable to the sound-evoked excitatory postsynaptic potentials (EPSPs) of large S1 fibers. They also shared other properties such as adaptive decline in amplitude, incremental and decremental responses, and off-suppression. The mean amplitude of the sound-evoked generator potentials in S2 fibers was linearly related to the rate of afferent firing. There was no apparent difference in the action potential threshold amplitude for spontaneous and sound-evoked generator potentials. It may be concluded that the generator potentials that underlie the spontaneous and sound-evoked firing of S2 fibers are produced by the release of transmitter by hair cells.