On the nature and origin of the calcium asymmetry arising during gravitropic response in etiolated pea epicotyls.
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Seven day old etiolated pea epicotyls were loaded symmetrically with 3H-indole 3-acetic acid (IAA) or 45Ca2+, then subjected to 1.5 hours of 1g gravistimulation. Epidermal peels taken from top and bottom surfaces after 90 minutes showed an increase in IAA on the lower side and of Ca2+ on the upper side. Inhibitors of IAA movement (TIBA, 9-hydroxyfluorene carboxylic acid) block the development of both IAA and Ca2+ asymmetries, but substances known to interfere with normal Ca2+ transport (nitrendipine, nisoldipine, Bay K 8644, A 23187) do not significantly alter either IAA or Ca2+ asymmetries. These substances, however, are active in modifying both Ca2+ uptake and efflux through oat and pea leaf protoplast membranes. We conclude that the 45Ca2+ fed to pea epicotyls occurs largely in the cell wall, and that auxin movement is primary and Ca2+ movement secondary in gravitropism. We hypothesize that apoplastic Ca2+ changes during graviresponse because it is displaced by H+ secreted through auxin-induced proton release. This proposed mechanism is supported by localized pH experiments, in which filter paper soaked in various buffers was applied to one side of a carborundum-abraded epicotyls. Buffer at pH 3 increases calcium loss from the side to which it is applied, whereas pH 7 buffer decreases it. Moreover, 10 micromolar IAA and 1 micromolar fusicoccin, which promote H+ efflux, increase Ca2+ release from pea epicotyl segments, whereas cycloheximide, which inhibits H+ efflux, has the reverse effect. We suggest that Ca2+ does not redistribute actively during gravitropism: the asymmetry arises because of its release from the wall adjacent to the region of high IAA concentration, proton secretion, and growth. Thus, the asymmetric distribution of Ca2+ appears to be a consequence of growth stimulation, not a critical step in the early phase of the graviresponse. (+info)
Effect of bile acids on absorption of nitrendipine in healthy subjects.
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AIMS: To examine whether bile acids such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) can influence the absorption of nitrendipine, a highly lipophilic calcium channel blocker. METHODS: Six healthy subjects received nitrendipine (10 mg) with and without UDCA (50 mg) and CDCA (200 and 600 mg) with an interval of 1 approximately 2 weeks between study phases. RESULTS: Bile acids decreased the Cmax (ng ml(-1)) [control 10.9 +/- 5.8 (mean+/- s.d.), UDCA 5.0 +/- 4.7 (95% confidence interval for difference; 3.9, 7.8, P = 0.0006), CDCA (600 mg) 5.0 +/- 3.9 (2.6, 9.2, P = 0.0059)] and AUC (ng ml(-1) h) [(control; 60 +/- 36, UDCA 15 +/- 13 (20, 73, P = 0.0064), CDCA (600 mg) 19 +/- 19 (21, 63, P = 0.0038)] of nitrendipine, while elimination half-life remained unchanged. CONCLUSIONS: These results suggest that the amount of nitrendipine absorbed was decreased when the drug was administered with UDCA and CDCA. (+info)
Synaptic plasticity in the trigeminal principal nucleus during the period of barrelette formation and consolidation.
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We examined whether the postsynaptic responses of cells in the principal sensory nucleus of the trigeminal nerve (PrV) are subject to long-term changes in synaptic strength, and if such changes were correlated the whisker-specific patterning during and just after the critical period for pattern formation. We used an in vitro brainstem preparation in which the trigeminal ganglion (TG) and PrV remained attached. By electrically activating TG afferents, we evoked large-amplitude extracellular field potentials. These responses were postsynaptic in origin and blocked by the glutamate antagonist, DNQX. At P1, a time when barrelettes are consolidating, high frequency stimulation of their afferents led to an immediate (<1 min) and long-lasting (> or =90 min) reduction (35%) in the amplitude of the evoked response. At P3-7, when the pattern of barrelettes have stabilized, the same form of tetanus led to an immediate and long-lasting increase (40%) in the amplitude of the response. Both forms of synaptic plasticity were mediated by the activation of L-type Ca(2+) channels. Application of the L-type channel blocker, nitrendipine, led to a complete blockade of any the tetanus induced changes. These associative processes may regulate the patterning and maintenance of whisker-specific patterns in the brainstem trigeminal nuclei. (+info)
Therapeutic effects of DCDDP, a calcium channel blocker, on chronic pulmonary hypertension in rat.
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To explore the effect of dimethyl 4-(2-chlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (DCDDP) on pulmonary hypertension (PH) induced by monocrotaline (MCT), the parameters of pulmonary hemodynamics, the contents of endothelin-like immunoreactivity, nitric oxide (NO), malondialdehyde, and superoxide dismutase in plasma and pulmonary homogenate were measured. DCDDP was administered in 5, 50, and 500 microg x kg(-1) x day(-1) ip doses, once a day for 28 days. The antiserotonin effect of DCDDP was investigated by using immunohistochemistry, image analysis, and cell culture technique. The results showed that pulmonary arterial pressure was significantly dropped and pulmonary resistance was decreased in DCDDP groups, compared with the MCT group. DCDDP had no influence on endothelin-like immunoreactivity levels in plasma and pulmonary homogenate but reduced the contents of NO, superoxide dismutase, and malondialdehyde in pulmonary homogenate enhanced by MCT. DCDDP also significantly inhibited the increase in numbers of 5-hydroxytryptamine (5-HT) and 5-HT receptor-positive cells in pulmonary tissue of PH rats induced by MCT. The proliferation and contraction of pulmonary arterial smooth muscle cells and the increase in concentration of free Ca(2+) in them evoked by 5-HT were inhibited significantly by DCDDP. The results suggest that DCDDP reduces the production of free radicals and content of 5-HT and 5-HT receptor and the increase in NO in pulmonary tissue, which underlies the mechanisms of DCDDP against MCT-induced PH. (+info)
Synaptic mechanisms regulating the activation of a Ca(2+)-mediated plateau potential in developing relay cells of the LGN.
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Using intracellular recordings in an isolated (in vitro) rat brain stem preparation, we examined the synaptic responses of developing relay neurons in the dorsal lateral geniculate nucleus (LGN). In newborn rats, strong stimulation of the optic tract (OT) evoked excitatory postsynaptic potentials (EPSPs) that gave rise to a sustained (300-1,300 ms), slow-decaying (<0.01 mV/s), depolarization (25-40 mV). Riding atop this response was a train of spikes of variable amplitude. We refer to this synaptically evoked event as a plateau potential. Pharmacology experiments indicate the plateau potential was mediated by the activation of high-threshold L-type Ca(2+) channels. Synaptic activation of the plateau potential relied on N-methyl-D-aspartate (NMDA) receptor-mediated activity and the spatial and/or temporal summation of retinally evoked EPSPs. Inhibitory postsynaptic responses (IPSPs) did not prevent the expression of the plateau potential. However, GABA(A) receptor activity modulated the intensity of optic tract stimulation needed to evoke the plateau potential, while GABA(B) receptor activity affected its duration. Expression of the plateau potential was developmentally regulated, showing a much higher incidence at P1-2 (90%) than at P19-20 (1%). This was in part due to the fact that developing relay cells show a greater degree of spatial summation than their mature counterparts, receiving input from as many as 7-12 retinal ganglion cells. Early spontaneous retinal activity is also likely to trigger the plateau potential. Repetitive stimulation of optic tract in a manner that approximated the high-frequency discharge of retinal ganglion cells led to a massive temporal summation of EPSPs and the activation of a sustained depolarization (>1 min) that was blocked by L-type Ca(2+) channel antagonists. These age-related changes in Ca(2+) signaling may contribute to the activity-dependent refinement of retinogeniculate connections. (+info)
Independent modulation of L-type Ca2+ channel in guinea pig ventricular cells by nitrendipine and isoproterenol.
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Dihydropyridine (DHP) Ca2+ channel blockers decrease L-type Ca2+ channel current (I(CaL)) by enhancing steady-state inactivation, whereas beta-adrenergic stimulation increases I(CaL) with small changes in the kinetics. We studied the effects of DHP Ca2+ channel blockers on cardiac I(CaL) augmented by beta-adrenergic stimulation. We recorded I(CaL) as Ba2+ currents (I(Ba)) from guinea pig ventricular myocytes using the whole-cell patch clamp technique. and compared the effects of nitrendipine (NIT) in the absence and presence of isoproterenol (1 microM, ISO) or forskolin (10 microM, FSK). Maximal I(Ba) elicited from a holding potential of -80 mV were diminished to 69.4+/-13.5% (mean and SE, n=5) of control by NIT (100 nM) and the diminished I(Ba) were increased to 180.3+/-23.2% of control by ISO in the presence of NIT, which was similar to the enhancement seen in the absence of NIT. NIT shifted the V(1/2) of the I(Ba) inactivation curve from -34.6+/-1.9 mV (n=5) to -48.7+/-1.2 mV, enhancing I(Ba) decay with shortening T(1/2) at -10 mV from 164.6+/-24.2 ms (n=7) to 105.4+/-15.2 ms. ISO elicited a small additional shift in the V(1/2) of I(Ba) inactivation in the same direction. ISO and FSK each slowed I(Ba) decay in the absence of NIT, but not in its presence. Thus, beta-adrenergic agonists increase and DHP Ca2+ channel blockers decrease the amplitude of cardiac I(CaL) independently and the kinetics of I(CaL) is determined mainly by the latter when these drugs coexist. (+info)
Hyposmotic shock stimulates insulin secretion by two distinct mechanisms. Studies with the betaHC9 cell.
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Exposure of betaHC9 cells to a Krebs-Ringer bicarbonate-HEPES buffer (KRBH) made hypotonic by a reduction of 25 mM NaCl resulted in a prompt stimulation of insulin release. The stimulation was transient, and release rates returned to basal levels after 10 min. The response resembles that of the first phase of glucose-stimulated insulin release. The response did not occur if the reduction in NaCl was compensated for by the addition of an equivalent osmolar amount of sorbitol, so the stimulation of release was due to the osmolarity change and not the reduction in NaCl. The hyposmotic shock released insulin in KRBH with or without Ca(2+). The L-type Ca(2+) channel blocker nitrendipine inhibited the response in normal KRBH but had no effect in KRBH without Ca(2+) despite the latter response being larger than in the presence of extracellular Ca(2+). Similar data were obtained with calciseptine, which also blocks L-type channels. The T-type Ca(2+) channel blocker flunarizine was without effect, as was the chloride channel blocker DIDS. In parallel studies, the readily releasable pool of insulin-containing granules was monitored. Immunoprecipitation of the target-SNARE protein syntaxin and co-immunoprecipitation of the vesicle-SNARE VAMP-2 was used as an indicator of the readily releasable granule pool. After hypotonic shock in the presence of extracellular Ca(2+), the amount of VAMP-2 coimmunoprecipitated by antibodies against syntaxin was much reduced compared with controls. Therefore, under these conditions, hypotonic shock stimulates exocytosis of the readily releasable pool of insulin-containing granules. No such reduction was seen in the absence of extracellular Ca(2+). In conclusion, after reexamination of the effect of hyposmotic shock on insulin secretion in the presence and absence of Ca(2+) (with EGTA in the medium), it is clear that two different mechanisms are operative under these conditions. Moreover, these two mechanisms may be associated with the release of two distinct pools of insulin-containing granules. (+info)
L-type calcium channel-mediated plateau potentials in barrelette cells during structural plasticity.
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Development and maintenance of whisker-specific patterns along the rodent trigeminal pathway depends on an intact sensory periphery during the sensitive/critical period in development. Barrelette cells of the brain stem trigeminal nuclei are the first set of neurons to develop whisker-specific patterns. Those in the principal sensory nucleus (PrV) relay these patterns to the ventrobasal thalamus, and consequently, to the somatosensory cortex. Thus PrV barrelette cells are among the first group of central neurons susceptible to the effects of peripheral damage. Previously we showed that membrane properties of barrelette cells are distinct as early as postnatal day 1 (PND 1) and remain unchanged following peripheral denervation in newborn rat pups (Lo and Erzurumlu 2001). In the present study, we investigated the changes in synaptic transmission. In barrelette cells of normal PND 1 rats, weak stimulation of the trigeminal tract (TrV) that was subthreshold for inducing Na(+) spikes evoked an excitatory postsynaptic potential-inhibitory postsynaptic potential (EPSP-IPSP) sequence that was similar to the responses seen in older rats (Lo et al. 1999). Infraorbital nerve transection at birth did not alter excitatory and inhibitory synaptic connections of the barrelette cells. These observations suggested that local neuronal circuits are already established in PrV at birth and remain intact after deafferentation. Strong stimulation of the TrV induced a sustained depolarization (plateau potential) in denervated but not in normal barrelette neurons. The plateau potential was distinct from the EPSP-IPSP sequence by 1) a sustained (>80 ms) depolarization above -40 mV; 2) a slow decline slope (<0.1 mV/ms); 3) partially or totally inactivated Na(+) spikes on the plateau; and 4) a termination by a steep decay (>1 mV/ms) to a hyperpolarizing membrane level. The plateau potential was mediated by L-type Ca(2+) channels and triggered by a N-methyl-D-aspartate (NMDA) receptor-mediated EPSP. gamma-aminobutyric acid-A (GABA(A)) receptor-mediated IPSP dynamically regulated the latency and duration of the plateau potential. These results indicate that after neonatal peripheral damage, central trigeminal inputs cause a large and long-lasting Ca(2+) influx through L-type Ca(2+) channels in barrelette neurons. Increased Ca(2+) entry may play a key role in injury-induced structural remodeling, and/or transsynaptic cell death. (+info)