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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemosensitive response of locus coeruleus (LC) neurones to changes in intracellular pH (pH(i)), extracellular pH (pH(o)) and molecular CO(2) were investigated using neonatal rat brainstem slices. A new technique was developed that involves the use of perforated patch recordings in combination with fluorescence imaging microscopy to simultaneously measure pH(i) and membrane potential (V(m)). Hypercapnic acidosis (15 % CO(2), pH(o) 6.8) resulted in a maintained fall in pH(i) of 0.31 pH units and a 93 % increase in the firing rate of LC neurones. On the other hand, isohydric hypercapnia (15 % CO(2), 77 mM HCO(3)(-), pH(o) 7.45) resulted in a smaller and transient fall in pH(i) of about 0.17 pH units and an increase in firing rate of 76 %. Acidified Hepes (N-2-hydroxyethylpiperazine-N'-2- ethanesulfonic acid)-buffered medium (pH(o) 6.8) resulted in a progressive fall in pH(i) of over 0.43 pH units and an increase in firing rate of 126 %. Isosmotic addition of 50 mM propionate to the standard HCO(3)(-)-buffered medium (5 % CO(2), 26 mM HCO(3)(-), pH(o) 7.45) resulted in a transient fall in pH(i) of 0.18 pH units but little increase in firing rate. Isocapnic acidosis (5 % CO(2), 7 mM HCO(3)(-), pH(o) 6.8) resulted in a slow intracellular acidification to a maximum fall of about 0.26 pH units and a 72 % increase in firing rate. For all treatments, the changes in pH(i) preceded or occurred simultaneously with the changes in firing rate and were considerably slower than the changes in pH(o). In conclusion, an increased firing rate of LC neurones in response to acid challenges was best correlated with the magnitude and the rate of fall in pH(i), indicating that a decrease in pH(i) is a major part of the intracellular signalling pathway that transduces an acid challenge into an increased firing rate in LC neurones.
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PMID:Role of intracellular and extracellular pH in the chemosensitive response of rat locus coeruleus neurones. 1204 54

We studied chemosensitive signaling in locus coeruleus (LC) neurons using both perforated and whole cell patch techniques. Upon inhibition of fast Na(+) spikes by tetrodotoxin (TTX), hypercapnic acidosis [HA; 15% CO(2), extracellular pH (pH(o)) 6.8] induced small, slow spikes. These spikes were inhibited by Co(2+) or nifedipine and were attributed to activation of L-type Ca(2+) channels by HA. Upon inhibition of both Na(+) and Ca(2+) spikes, HA resulted in a membrane depolarization of 3.52 +/- 0.61 mV (n = 17) that was reduced by tetraethylammonium (TEA) (1.49 +/- 0.70 mV, n = 7; P < 0.05) and absent (-0.97 +/- 0.73 mV, n = 7; P < 0.001) upon exposure to isohydric hypercapnia (IH; 15% CO(2), 77 mM HCO(3)(-), pH(o) 7.45). Either HA or IH, but not 50 mM Na-propionate, activated Ca(2+) channels. Inhibition of L-type Ca(2+) channels by nifedipine reduced HA-induced increased firing rate and eliminated IH-induced increased firing rate. We conclude that chemosensitive signals (e.g., HA or IH) have multiple targets in LC neurons, including TEA-sensitive K(+) channels and TWIK-related acid-sensitive K(+) (TASK) channels. Furthermore, HA and IH activate L-type Ca(2+) channels, and this activation is part of chemosensitive signaling in LC neurons.
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PMID:Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K+ and Ca2+ channels. 1238 81

It recently has been shown that whole cell calcium and sodium currents are modulated by CO(2)/HCO(3)(-)-buffered saline. While the bicarbonate ion, but not CO(2), has been proven to modulate calcium currents, this information is lacking for sodium currents. Furthermore, it is not known whether the strength of modulation dependents on the bicarbonate concentration or whether it is an all-or-nothing phenomenon. To answer these questions, we used the whole cell voltage-clamp technique on freshly isolated hippocampal CA1 neurons from the rat. A voltage step from -130 to -20 mV elicited a sodium current with an amplitude of -5.1 +/- 0.5 nA (mean +/- SE, n = 17) when cells were superfused with HEPES-buffered saline. The amplitude of this current increased during a subsequent superfusion with solutions containing increasing amounts of bicarbonate and CO(2) (%CO(2)/mM HCO(3)(-): 2.5/5.6; 5.0/18; 10/37), with a maximal increment in 10% CO(2)/37 mM HCO(3)(-) of -6.9 +/- 0.8 nA. The increase in amplitude was associated with a linear negative shift (slope: -0.7 mV/mM HCO(3)(-)) of the potential of half-maximal activation (DeltaV(h,a): -19.4 +/- 1.8 mV in 10% CO(2)) but not with an alteration in the maximal conductance (g(max): HEPES: 203.1 +/- 21.0 nS and 10% CO(2)/37 mM HCO(3)(-): 207.3 +/- 21.3 nS). In addition, the potential of half-maximal inactivation (V(h,i)) shifted to more negative potentials (slope: -0.6 mV/mM HCO(3)(-)) with increasing amounts of bicarbonate and CO(2) (HEPES: -53.6 +/- 11.8 mV; 10% CO(2)/37 mM HCO(3)(-): -69.8 +/- 2.1 mV), making the amplitude of the current highly sensitive for small potential changes at resting membrane potential. The same negative shift in voltage dependence arose when cells were exposed to solutions with different amounts of bicarbonate (5.6; 18; 26 mM) but constant CO(2) (5%) with slope rates of -0.5 mV/mM HCO(3)(-) for V(h,a) and -0.5 mV/mM HCO(3)(-) for V(h,i). Again, there was no correlation between bicarbonate concentration and the size of g(max). When currents were evoked in solutions containing a constant concentration (18 mM) of bicarbonate but different amounts of CO(2) (2.5; 5.0 10%), no significant changes have been observed. The present data demonstrate that bicarbonate ions, and not CO(2), modulate voltage-gated sodium currents in a concentration-dependent manner. Because the amplitude of the sodium current becomes highly sensitive to membrane potential changes concomitant with increased bicarbonate amounts, this may be critical for the excitability of the neuronal network in situations (like metabolic acidosis, respiratoric alkalosis and hypercapnia) in which the concentration of this ion can alter.
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PMID:Relation between bicarbonate concentration and voltage dependence of sodium currents in freshly isolated CA1 neurons of the rat. 1261 66

The cardiorespiratory responses were examined in yellowtail, Seriola quinqueradiata exposed to two levels of hypercapnia (seawater equilibrated with a gas mixture containing 1% CO(2) (water PCO(2) = 7 mmHg) or 5% CO(2) (38 mmHg)) for 72 hr at 20 degrees C. Mortality was 100% within 8 hr at 5% CO(2), while no fish died at 1% CO(2). No cardiovascular variables (cardiac output, Q; heart rate, HR; stroke volume, SV and arterial blood pressure, BP) significantly changed from pre-exposure values during exposure to 1% CO(2). Arterial CO(2) partial pressure (PaCO(2)) significantly increased (P < 0.05), reaching a new steady-state level after 3 hr. Arterial blood pH (pHa) decreased initially (P < 0.05), but was subsequently restored by elevation of plasma bicarbonate ([HCO(3)(-)]). Arterial O(2) partial pressure (PaO(2)), oxygen content (CaO(2)), and hematocrit (Hct) were maintained throughout the exposure period. In contrast, exposure to 5% CO(2) dramatically reduced Q (P < 0.05) through decreasing SV (P < 0.05), although HR did not change. BP was transiently elevated (P < 0.05), followed by a precipitous fall before death. The pHa was restored incompletely despite a significant increase in [HCO(3)(-)]. PaO(2) decreased only shortly before death, whereas CaO(2) kept elevated due to a large increase in Hct (P < 0.05). We tentatively conclude that cardiac failure is a primary physiological disorder that would lead to death of fish subjected to high environmental CO(2) pressures.
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PMID:Effects of lethal levels of environmental hypercapnia on cardiovascular and blood-gas status in yellowtail, Seriola quinqueradiata. 1271 43

Putative chemoreceptors in the solitary complex (SC) are sensitive to hypercapnia and oxidative stress. We tested the hypothesis that oxidative stress stimulates SC neurons by a mechanism independent of intracellular pH (pH(i)). pH(i) was measured by using ratiometric fluorescence imaging microscopy, utilizing either the pH-sensitive fluorescent dye BCECF or, during whole cell recordings, pyranine in SC neurons in brain stem slices from rat pups. Oxidative stress decreased pH(i) in 270 of 436 (62%) SC neurons tested. Chloramine-T (CT), N-chlorosuccinimide (NCS), dihydroxyfumaric acid, and H(2)O(2) decreased pH(i) by 0.19 +/- 0.007, 0.20 +/- 0.015, 0.15 +/- 0.013, and 0.08 +/- 0.002 pH unit, respectively. Hypercapnia decreased pH(i) by 0.26 +/- 0.006 pH unit (n = 95). The combination of hypercapnia and CT or NCS had an additive effect on pH(i), causing a 0.42 +/- 0.03 (n = 21) pH unit acidification. CT slowed pH(i) recovery mediated by Na(+)/H(+) exchange (NHE) from NH(4)Cl-induced acidification by 53% (n = 20) in CO(2)/HCO(3)(-)-buffered medium and by 58% (n = 10) in HEPES-buffered medium. CT increased firing rate in 14 of 16 SC neurons, and there was no difference in the firing rate response to CT with or without a corresponding change in pH(i). These results indicate that oxidative stress 1). decreases pH(i) in some SC neurons, 2). together with hypercapnia has an additive effect on pH(i), 3). partially inhibits NHE, and 4) directly affects excitability of CO(2)/H(+)-chemosensitive SC neurons independently of pH(i) changes. These findings suggest that oxidative stress acidifies SC neurons in part by inhibiting NHE, and this acidification may contribute ultimately to respiratory control dysfunction.
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PMID:Oxidative stress decreases pHi and Na(+)/H(+) exchange and increases excitability of solitary complex neurons from rat brain slices. 1466 60

Using degenerate primers, followed by 3' and 5' RACE and "long" PCR, a continuous 4050-bp cDNA was obtained and sequenced from rainbow trout (Oncorhynchus mykiss) gill. The cDNA included an open reading frame encoding a deduced protein of 1088 amino acids. A BLAST search of the GenBank protein database demonstrated that the trout gene shared high sequence similarity with several vertebrate Na(+)/HCO(3)(-) cotransporters (NBCs) and in particular, NBC1. Protein alignment revealed that the trout NBC is >80% identical to vertebrate NBC1s and phylogenetic analysis provided additional evidence that the trout NBC is indeed a homolog of NBC1. Using the same degenerate primers, a partial cDNA (404 bp) for NBC was obtained from eel (Anguilla rostrata) kidney. Analysis of the tissue distribution of trout NBC, as determined by Northern blot analysis and real-time PCR, indicated high transcript levels in several absorptive/secretory epithelia including gill, kidney and intestine and significant levels in liver. NBC mRNA was undetectable in eel gill by real-time PCR. In trout, the levels of gill NBC1 mRNA were increased markedly during respiratory acidosis induced by exposure to hypercarbia; this response was accompanied by a transient increase in branchial V-type H(+)-ATPase mRNA levels. Assuming that the branchial NBC1 is localised to basolateral membranes of gill cells and operates in the influx mode (HCO(3)(-) and Na(+) entry into the cell), it would appear that in trout, the expression of branchial NBC1 is transcriptionally regulated to match the requirements of gill pHi regulation rather than to match trans-epithelial HCO(3)(-) efflux requirements for systemic acid-base balance. By analogy with mammalian systems, NBC1 in the kidney probably plays a role in the tubular reabsorption of both Na(+) and HCO(3)(-). During periods of respiratory acidosis, levels of renal NBC1 mRNA increased (after a transient reduction) in both trout and eel, presumably to increase HCO(3)(-) reabsorption. This strategy, when coupled with increased urinary acidification associated with increased vacuolar H(+)-ATPase activity, ensures that HCO(3)(-) levels accumulate in the body fluids to restore pH.
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PMID:Integrated responses of Na+/HCO3- cotransporters and V-type H+-ATPases in the fish gill and kidney during respiratory acidosis. 1472 54

Environmental hypercapnia induces a respiratory acidosis that is usually compensated within 24-96 h in freshwater fish. Water ionic composition has a large influence on both the rate and degree of pH recovery during hypercapnia. Waters of the Amazon are characteristically dilute in ions, which may have consequences for acid-base regulation during environmental hypercapnia in endemic fishes. The armoured catfish Liposarcus pardalis, from the Amazon, was exposed to a water P(CO(2)) of 7, 14 or 42 mmHg in soft water (in micromol l(-1): Na(+), 15, Cl(-), 16, K(+), 9, Ca(2+), 9, Mg(2+), 2). Blood pH fell within 2 h from a normocapnic value of 7.90+/-0.03 to 7.56+/-0.04, 7.34+/-0.05 and 6.99+/-0.02, respectively. Only minor extracellular pH (pH(e)) recovery was observed in the subsequent 24-96 h. Despite the pronounced extracellular acidosis, intracellular pH (pH(i)) of the heart, liver and white muscle was tightly regulated within 6 h (the earliest time at which these parameters were measured) via a rapid accumulation of intracellular HCO(3)(-). While most fish regulate pH(i) during exposure to environmental hypercapnia, the time course for this is usually similar to that for pH(e) regulation. The degree of extracellular acidosis tolerated by L. pardalis, and the ability to regulate pH(i) in the face of an extracellular acidosis, are the greatest reported to date in a teleost fish. The preferential regulation of pH(i) in the face of a largely uncompensated extracellular acidosis in L. pardalis is rare among vertebrates, and it is not known whether this is associated with the ability to air-breathe and tolerate aerial exposure, or living in water dilute in counter ions, or with other environmental or evolutionary selective pressures. The ubiquity of this strategy among Amazonian fishes and the mechanisms employed by L. pardalis are clearly worthy of further study.
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PMID:Limited extracellular but complete intracellular acid-base regulation during short-term environmental hypercapnia in the armoured catfish, Liposarcus pardalis. 1532 14

The South American lungfish (Lepidosiren paradoxa) has well-developed lungs and highly reduced gills. To evaluate acid-base regulation, we applied hypercarbia while blood gases and pulmonary ventilation were measured for up to 48 h. Dorsal aortic blood was analyzed, and pulmonary ventilation was measured by pneumotachography. Two protocols were used: (1) normocarbia (control) followed by aquatic hypercarbia (7% CO2 approximately 49 mmHg), gas phase normocarbic; and (2) normocarbia (control) followed by combined aquatic/gas phase hypercarbia (7% CO2). Normocarbic values were pHa~7.5, Paco2 approximately 17 mmHg, and [HCO-3]pl approximately 22 mM. For protocol 1, the first hour of exposure increased Paco2 from 17.0 to 37.4 mmHg, and pHa fell to 7.21 and remained there for the rest of the experiment. At 3 h, pulmonary ventilation reached sixfold the normocarbic value but then decreased. For protocol 2, combined gas phase/water hypercarbia had a large effect on acid-base status. Thus, Paco2 increased gradually to 74 mmHg (pHa=7.15) at 48 h. At 3 h, ventilation reached a sixfold increase relative to normocarbic control but then rose further to a 60-fold peak at 6 h, followed by a gradual decline. As in some salamanders and air-breathing teleosts, there was no evidence of active extracellular modulation bicarbonate.
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PMID:Acid-base regulation in the South American lungfish Lepidosiren paradoxa: effects of prolonged hypercarbia on blood gases and pulmonary ventilation. 1622 30

The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore, we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar-Hannover rats were exposed to either hypercapnia and hypoxia [8% CO(2) and 13% O(2) (hypercapnic, n = 6) or normal air (controls, n = 6)] in an environmental chamber for 10 days and were killed under the same atmosphere. In hypercapnic rats, arterial pH was lower than controls (7.31 +/- 0.01 vs. 7.39 +/- 0.01, P = 0.03), blood HCO(3)(-) concentration was increased (42 +/- 0.9 vs. 32 +/- 0.24 mM, P < 0.001), arterial Pco(2) was increased (10.76 +/- 0.4 vs. 7.20 +/- 0.4 kPa, P < 0.001), and plasma chloride concentration was decreased (92.2 +/- 0.7 vs. 97.2 +/- 0.5 mM, P < 0.001). Plasma aldosterone levels were unchanged. In the proximal tubule, immunoblotting showed an increased expression of sodium/bicarbonate exchanger protein (188 +/- 22 vs. 100 +/- 11%, P = 0.005), confirmed by immunohistochemistry. Total Na/H exchanger protein expression in the cortex was unchanged by immunoblotting (119 +/- 10 vs. 100 +/- 11%, P = 0.27) and immunohistochemistry. In the cortex, the abundance of pendrin was decreased (51 +/- 9 vs. 100 +/- 7%, P = 0.003) by immunoblotting. Immunohistochemistry revealed that this decrease was clear in both cortical collecting ducts (CCDs) and connecting tubules (CNTs). This demonstrates that pendrin expression can be regulated in acidotic animals with no changes in aldosterone levels and no external chloride load. This reduction of pendrin expression may help in redirecting the CNT and CCD toward chloride excretion and bicarbonate reabsorption, contributing to the increased plasma bicarbonate and decreased plasma chloride of chronic respiratory acidosis.
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PMID:Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and adaptation of the proximal tubule. 1718 33

It is common to see chapters on acid-base physiology state that the goal of acid-base regulatory mechanisms is to maintain the pH of arterial plasma and not arterial Pco(2) (Pa(CO(2))) or plasma HCO(3). A hypothetical situation in which the Pa(CO(2)) of arterial plasma is 80 mmHg and the plasma HCO(3) concentration is 48 mM is presented and analyzed to get over this misconception. As per the modified Henderson equation, the pH of arterial plasma would be 7.4; however, we explain that this may be associated with intracellular acidosis due to intracellular hypercapnia and that derangement of homeostasis is evident from the occurrence of respiratory depression and, eventually, coma in the patient described. This suggests that the ultimate goal of acid-base regulatory mechanisms is not just the maintenance of the pH of arterial plasma but the maintenance of the steady-state pH of intracellular fluid as well.
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PMID:What is the ultimate goal in acid-base regulation? 1732 83


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