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G Hagiwara

Publications and source records attributed to G Hagiwara.

8 recordsLinked to original sources
PubMed1991

Cystic fibrosis, the CFTR, and rectifying Cl- channels.

The human genetic disease cystic fibrosis is caused by a single defective gene on chromosome 7 that codes for a 1480 amino acid protein called the cystic fibrosis transmembrane conductance regulator (CFTR). The defect causes a profound reduction of Cl- permeability in several tissues, which in turn impairs salt absorption and fluid secretion. A 25-80 pS, rectifying Cl- channel has been targeted as the exclusive or primary channel affected in CF. However, we have found no evidence for significant activation or spontaneous activity of this channel in cell-attached patches of normal lymphoblasts or dog tracheal cells. However, in dog tracheal cells, we find lower conductance, linear Cl- channels that are spontaneously active in unstimulated cells and may show increased activity in stimulated cells. Attempts to correlate the expression of mRNA for the CFTR protein in various types of cells with the presence of the rectifying Cl- channel show a lack of correlation: i.e., depolarization-activated rectifying Cl- channesl have been found in excised, inside-out patches from all cell types that we have examined to date, but the CFTR mRNA has so far only been detected in a subset of epithelial cells.

Animals↗
PubMed1989

Patch-clamp study of cultured human sweat duct cells: amiloride-blockable Na+ channel.

The reabsorptive duct of the eccrine sweat gland has a large transepithelial conductance consisting mainly of a high conductance to Cl- and a smaller, amiloride-blockable Na+ conductance (Bijman and Frömter 1986; Quinton 1986). Cells have been cultured from sweat ducts and their properties previously studied in Ussing chambers (Pedersen 1988) and with microelectrodes (Jones et al. 1988). We have now studied the ion channels present in excised, inside-out patches of human cultured sweat duct cells, and find a marked predominance of linear, 15 pS, amiloride-blockable, low selectivity, Na+ channels. Such channels were seen in 54/92 (59%) of the patches, with up to 7 channels recorded in a single patch. Other channel types were seen at much lower densities. The prevalence of an amiloride-blockable Na+ channel in cultured duct cells clearly distinguishes these cells from cultured sweat gland secretory cells, which lack such a channel.

Amiloride↗
PubMed1989

Ion channels in normal human and cystic fibrosis sweat gland cells.

Single-channel patch-clamp techniques were used to study the population of apical membrane ion channels in cultured sweat gland secretory cells from normal and cystic fibrosis subjects. Four types of anion channels and two types of cation channels were found. At physiological voltages, anion channels had chord conductances of 10, 18, 24, and greater than 200 pS. All had linear current-voltage relations except the 24 pS channel, which showed outward rectification. Cation channels had chord conductances of 5 and 18 pS, were linear, and were nonselective for a variety of cations. Channel types and proportions were equivalent in control, cystic fibrosis, and cystic fibrosis heterozygote cells. Beyond showing that the distribution of channel types remains unchanged in cystic fibrosis cells, the data provide a basis for comparison with cells cultured under different conditions, with other cell types, and with native tissues.

Adolescent↗
PubMed1987

Hyposecretion of beta-adrenergically induced sweating in cystic fibrosis heterozygotes.

In order to determine if expression of the cystic fibrosis gene can be detected in heterozygotes, we determined sweat responses induced by local stimulation with cholinergic and beta-adrenergic agents for 20 heterozygotes, 19 age- and sex-matched controls, and five subjects with cystic fibrosis. Active sweat glands were counted and sweat droplets were collected in constant bore capillaries and measured optically. Each subject was tested two to six times. The central finding was that the sweat response of carriers was significantly lower than controls to beta-adrenergic stimulation (p = 0.0013, two-tailed t test; p less than 0.02, Mann-Whitney U), while cystic fibrosis homozygotes did not sweat at all. In contrast, the cholinergic sweat responses did not differ between carriers and controls. For both groups the correlation between cholinergic and beta-adrenergic sweating was positive, but a linear regression of beta-adrenergic sweat responses as a function of cholinergic sweat responses yielded slopes that were significantly different for the two groups. The ratio of beta-adrenergic to cholinergic sweating was plotted for each subject; the mean ratio of the carriers was approximately half of the mean for the controls (p = 0.0002 using t test or p less than 0.002 using the Mann-Whitney U). Our results confirm previous studies and provide new evidence that carriers have, on average, a beta-adrenergically stimulated secretory response that is significantly reduced relative to the control response.

Adrenergic beta-Agonists↗
PubMed1985

Segmental differences in pathways between crayfish giant axons and fast flexor motoneurons.

We have used electrophysiological techniques to document segmental differences in the pathways between the giant, escape command axons, lateral giants (LG) and medial giants (MG), and the nongiant, fast flexor (FF) motoneurons. We found no difference in the input from LG and MG axons to FF motoneurons in the posterior (4th and 5th) ganglia. Since flexor motor output in these segments would be inconsistent with the LG-evoked behavior pattern, this finding was puzzling. Electromyographic (EMG) recordings during escape responses by intact unrestrained animals confirm that the FF muscles innervated by the posterior ganglia are not excited during LG-mediated tailflips, but are excited during MG-mediated tailflips. In the 2nd and 3rd ganglia, the command axons fire the FF motoneurons with high probability, in part via electrical excitatory postsynaptic potentials (EPSPs) from premotor neurons, the segmental giants (SG). In the 4th and 5th ganglia, the equivalent pathway is much less effective. Single, directly elicited impulses in SGs in ganglia 2 and 3 fire their respective FF motoneurons with high probability, while those in ganglia 4 and 5 rarely fire FF motoneurons. The command axons fire the SGs reliably in all segments. The amplitude of the SG-evoked EPSP in FF motoneurons is significantly smaller in posterior vs. anterior ganglia. For technical reasons, we are unable to present conclusive evidence on ganglionic variations in FF-motoneuron thresholds. The FF motoneurons receive additional excitatory input from intersegmental interneurons recruited by the command neurons. Motoneurons in ganglia 4 and 5 are excited by large interneurons that do not synapse on motoneurons in ganglia 2 and 3, but this additional input is not sufficient to compensate for the weaker effect of SG input. Unlike the all-or-none segmental differences demonstrated previously for the LG-to-motor giant pathway (24), the SG-to-FF pathway changes gradually, retains significant though subthreshold strength in posterior ganglia, and is common to both LGs and MGs. These features provide opportunities for variation in the spatial patterning of flexion and in the resulting escape trajectories.

Animals↗
PubMed1982

Segmental giant: evidence for a driver neuron interposed between command and motor neurons in the crayfish escape system.

1. The giant command neurons for tailflip escape behavior in crayfish have been thought to excite the nongiant fast flexor (tailflip producing) motor neurons (FFs) via monosynaptic connections. We show here that excitation of FFs instead occurs via a bilateral pair of segmental giant neurons (SGs) interposed between the command axons and FFs in each segment. 2. Anatomically, the SGs appear to make numerous contacts with ipsilateral command axons and FFs and fewer contacts contralaterally. In contrast, the command axons have only sparse direct connections to the FFs. An SG has an axon in the ipsilateral first ganglionic root and may be a modified swimmeret motor neuron. 3. Each SG is depolarized well beyond threshold by the firing of an ipsilateral command axon and is depolarized to near threshold by the firing of a contralateral command axon. The synapses between command axons and SGs are electrical and probably rectifying. 4. Each FF is excited to a level near firing threshold by the SG ipsilateral to its axon and is excited weakly by the contralateral SG. The synapses between SGs and FFs are electrical and nonrectifying. 5. Variations in excitatory postsynaptic potentials (EPSPs) recorded in FFs during prolonged, high-frequency firing of the command axons can be accounted for by refractoriness of SG spikes, as opposed to refractoriness of dendritic branch spikes as had previously been delivered. 6. These findings illustrate the limitations of conventional tests for monosynapticity. 7. The functional significance of having driver neurons interposed between command neurons and motor neurons is discussed.

Animals↗
PubMed1978

Durations of unitary synaptic potentials help time a behavioral sequence.

Recordings in identified neurons and muscles that mediate crayfish tailflips reveal inhibitory postsynaptic potentials of two distinct durations. Those of long duration are recorded in five classes of cells in the flexion circuit, while those of short duration are recorded in three classes of cells in the extension circuit. The durations of the inhibitory postsynaptic potentials are matched to the durations of inhibition required by the different phases of the behavior.

Animals↗