[-174 G/C polymorphism of interleukin 6 gene in women with type 1 diabetes].

Background: A polymorphism located in the promoter region (-174 G/C) of interleukin 6 (IL-6) has been linked to early onset of type 1 diabetes (T1D) and increased body mass index (BMI).

Aim: To evaluate the possible association of this -IL-6 gene 174 GIC polymorphism with T1D, BMI and metabolic control in T1D patients in a case-control study.

Patients And Methods: -174 G I C polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 145 women with T1D and 103 healthy controls.

Fifty years of progress in carotid body physiology--invited article.

Research on arterial chemoreceptors, particularly on the carotid body, has been fruitful in the last fifty years, to which this review is addressed. The functional anatomy of the organ appears to be well established. The biophysical bases by which glomus cells transduce chemical changes in the milieu intérieur (hypoxia, hypercapnia, acidosis) into electrical and biochemical changes in glomus cells have received much attention.

Mechanical sensitivity of carotid body glomus cells.

Cultured glomus cells from rat carotid bodies were prepared for optical studies of intracellular calcium using the Fura-2 dye. The baseline calcium had a mean of about 40 nM showing either a relatively steady level or large calcium spikes. Some cells did not show measurable levels of [Ca(2+)](i).

Electric synapses in the carotid body-nerve complex.

Slices of rat carotid bodies, or cultured glomus cells, were used to study intercellular coupling. This phenomenon occurs because gap junctions allow passage of currents and dyes from one cell to another. There is a two-way resistive coupling between glomus cells (GC/GC coupling), which is accompanied by activity of intercellular channels.

Chemical and electric transmission in the carotid body chemoreceptor complex.

Carotid body chemoreceptors are complex secondary receptors. There are chemical and electric connections between glomus cells (GC/GC) and between glomus cells and carotid nerve endings (GC/NE). Chemical secretion of glomus cells is accompanied by GC/GC uncoupling.

Electrophysiological properties of rat nodose ganglion neurons co-transplanted with carotid bodies into the chick chorioallantoic membrane.

The electrophysiological properties of nodose ganglion neurons were evaluated immediately after removing nodose ganglia from young adult rats and 3 to 10 days after nodose ganglia implantation -either alone or co-implanted with carotid bodies- onto the chick chorioallantoic membrane. Implanted and co-implanted nodose neurons were less excitable than acutely recorded nodose neurons. Co-implanted neurons also showed reduced amplitudes for both action potentials and spike after-hyperpolarizations relative to those found in.

Effects of prolonged hypobaric hypoxia on carotid nerve endings and glomus cells. Changes in intercellular coupling.

Carotid bodies were removed from anesthetized rats kept under normobaric (640 Torr) and hypobaric conditions (380 Torr for 2-3 weeks). Slices (100-150 microm) of the organ were viewed under an inverted microscope for simultaneous stimulation and recording of coupled glomus cells and carotid nerve endings. The latter were identified by their more negative Em, high input resistance (Ro) and time-dependent rectification in response to negative current pulses.

Calcium channels of cultured rat glomus cells in normoxia and acute hypoxia.

Glomus cells harvested from Wistar rat carotid bodies were cultured for 4 to 7 days. Inward calcium currents elicited by voltage ramps (0.24 V/s) or pulses were recorded during voltage-clamping in the whole-cell and perforated patch configurations.

Effects of hypoxia and putative transmitters on [Ca2+]i of rat glomus cells.

Dissociated rat glomus cells were loaded with Fura-2 AM to study the effects of hypoxia, and carotid body transmitters on intracellular calcium, [Ca2+]i. The mean control [Ca2+]i was 55 nM in isolated cells and 67 nM in clusters. The following procedures changed [Ca2+]i:0[Ca2+]o+EGTA reduced [Ca2+]i by about 50%, suggesting that the remaining calcium originated from intracellular organelles.

Behavior of junction channels between rat glomus cells during normoxia and hypoxia.

The activity of gap junction channels between cultured and clustered carotid body glomus cells of the rat was studied with dual voltage clamping during normoxia (PO(2) 300 Torr) and hypoxia induced by sodium dithionite (Na(2)S(2)O(4)) or 100% N(2). Na(2)S(2)O(4) reduced the saline PO(2) to approximately 10 Torr, whereas 100% N(2) reduced ambient O(2) to approximately 60 Torr. The following observations were made.

Acidic regulation of junction channels between glomus cells in the rat carotid body. Possible role of [Ca(2+)](i).

The purpose of this work was to characterize the gap junctions between cultured glomus cells of the rat carotid body and to assess the effects of acidity and accompanying changes in [Ca(2+)](i) on electric coupling. Dual voltage clamping of coupled glomus cells showed a mean macrojunctional conductance (G(j)) of 1.16 nS+/-0.

Short- and long-term regulation of rat carotid body gap junctions by cAMP. Identification of connexin43, a gap junction subunit.

Intact and cultured carotid bodies (CBs) of the rat were used in this study. Applications of membrane-permeant db-cAMP to cultured carotid bodies increased electric coupling between most glomus cells (increasing junctional conductance) probably by opening preformed intercellular channels. This a short-term effect of the nucleotide, increasing gating between glomus cells.

Carotid body gap junctions: secretion of transmitters and possible electric coupling between glomus cells and nerve terminals.

It is proposed that intercellular coupling between glomus cells and carotid nerve terminals form an integral part of the chemoreceptor process. Coupling is possible because gap junctions occur between these elements. At rest, most glomus cells would be coupled.

Carotid body glomus cells: chemical secretion and transmission (modulation?) across cell-nerve ending junctions.

Glomus cells of the carotid body contain and secrete chemicals during 'natural' stimulation (hypoxia, hypercapnia and acidity), thus, the birth of the 'transmitter hypothesis of chemoreception'. Released chemicals would cross the synaptic cleft between glomus cells and carotid nerve terminals to depolarize the nerve ending membrane during excitation and hyperpolarize the membrane during inhibition. The main problem with this hypothesis is that specific synaptic blockers modify but do not block the effects of natural stimulation, while blocking the effects of the putative transmitters.

Effects of hypoxia induced by Na2S2O4 on intracellular calcium and resting potential of mouse glomus cells.

Isolated and cultured glomus cells, obtained from mouse carotid bodies, were superfused with Ham's F-12 equilibrated with air (mean PO2, 119 Torr; altitude 1350 m). [Ca2+]o was 3.0 mM.

Hypoxia induced by Na2S2O4 increases [Na+]i in mouse glomus cells, an effect depressed by cobalt. Experiments with Na+-selective microelectrodes and voltage-clamping.

The intracellular sodium concentration ([Na+]i) and resting potential (Em) of cultured mouse glomus cells (clustered and isolated) were simultaneously measured with intracellular Na+-sensitive and conventional, KCl-filled, microelectrodes. Results obtained in clustered and isolated cells were similar. During normoxia (PO2 122 Torr), [Na+]i was 12-13 mM corresponding to a Na+ equilibrium potential (ENa) of about 58 mV.

Modulation of junctional conductance between rat carotid body glomus cells by hypoxia, cAMP and acidity.

Short-term cultures of glomus cells (up to seven days), were employed to study intercellular electrical communications. Bidirectional electric coupling was established under current clamping after impaling two adjacent glomus cells with microelectrodes, and alternate stimulation and recording. Their resting potential (Vm) and input resistance (Ro) were thus measured.

Effects of calcium on the electric coupling of carotid body glomus cells.

Pairs of electrically coupled glomus cells from rat carotid bodies were impaled with microelectrodes. In the current clamp mode, intracellular stimulation and recording established the coupling coefficient (KC), across the intercellular junctions. About 80% of 26 pairs uncoupled during exposure to 9.

Effects of hypoxia on the intercellular channel activity of cultured glomus cells.

Dual voltage clamp experiments have shown that hypoxia induced by Na-dithionite or N2 reduced junctional macroconductance (Gj) in about 70% of cultured and coupled glomus cell pairs while increasing it in the rest. To explore possible mechanisms for these effects, we studied the activity of gap junction channels under similar conditions. The calculated single channel conductances (gj) fell into two categories.

Possible role of coupling between glomus cells in carotid body chemoreception.

Glomus cells of the carotid body are dye and electrically coupled due to the presence of gap junctions between them. During stimulation by hypoxia, hypercapnia and acidity, about 70% of the cells uncouple to various degrees, whereas the rest either develop tighter coupling or are unaffected. Similar results have been obtained with exogenous administrations of naturally present transmitters such as dopamine and cholinergic substances.

Effects of hypoxia on the intracellular K+ of clustered and isolated glomus cells of mice and rats.

Carotid bodies of rats and mice were used to measure the intracellular potassium activity, ai(K), of clustered and isolated glomus cells normally oxygenated (pO2 102-139 Torr), and during hypoxia (pO2 2-82 Torr) induced by Na-dithionite. ai(K) was measured with intracellular ion-selective microelectrodes, and the resting potential (EM) with KCl-filled micropipettes. Under normoxia, the ai(K) of clustered cells in both species was higher than that of isolated cells.