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P Georgiou

Publications and source records attributed to P Georgiou.

27 records · Page 2Linked to original sources

A delayed all-or-none hyperpolarisation induced by a single Ca action potential in hamster eggs.

A transient change of membrane potential and resistance could be evoked after a long latency (ca. 9 s) by a single calcium action potential in some unfertilized hamster eggs. The estimated reversal potential for the delayed response was close to EK supporting the conclusion that K channels were opened indirectly by the Ca2+ influx through voltage-gated channels. A second action potential elicited after the first did not induce a similar response. A number of treatments (insertion of a Ca2+ pipette, application of Na+-free solution, La3+ or high external pH) likely to raise [Ca2+]i also induced similar large changes of potential and resistance after which a single action potential failed to evoke a large delayed response. The evidence indicates that a small rise in [Ca2+]i activates a slow process leading to a further large increase in [Ca2+]i.

Action Potentials↗

On the mechanism of a pH-induced rise in membrane potassium conductance in hamster eggs.

1. The effect of external pH (pHo) on the membrane potential and resistance of unfertilized zona-free hamster eggs was investigated by intracellular recording techniques. 2. A hyperpolarization of the hamster egg membrane was induced by raising the extracellular pH above 8.0. This hyperpolarization was accompanied by a rise in membrane conductance and was reversible by washing the egg. 3. The estimated value of the reversal potential of the hyperpolarizing response to a solution with pHo 9.5 was about -85 mV. The membrane potential changed linearly with log [K+]o with a slope of 43 +/- 2 mV (mean +/- S.D.; n = 4) for a 10-fold change in [K+]o, while it was unaltered by the removal of Cl- from the solution. 4. The amplitude of the pHo-induced hyperpolarization decreased substantially as [Ca2+]o was lowered from 20 to 1 mM. Sr2+ could substitute for Ca2+ in sustaining the response to high pHo, whereas Ba2+ or Mg2+ could not. 5. Injection of the Ca2+ chelator EGTA into the egg prevented the pHo-induced hyperpolarization suggesting that a rise in [Ca2+]i is required. 6. The rate of rise of Ca2+ action potentials was reversibly enhanced by raising pHo. However, influx through the voltage-gated Ca2+ channels is not involved in initiation and maintenance of the pHo-induced response, as responses were not affected by the Ca2+ channel blocker La3+. 7. The duration of the hyperpolarization evoked by intracellular Ca2+ injection in eggs bathed in normal solution or Na+-free solution was greatly prolonged by raising pHo. 8. It is suggested that a rise in external pH produces an increase in [Ca2+]i, activating a Ca2+-mediated K+ conductance which hyperpolarizes the egg membrane. 9. It is concluded that both a Na+-Ca2+ exchange system and a Ca2+ pump are responsible for Ca2+ extrusion and that inhibition of the Ca2+ pump by high pHo is the chief mechanism underlying the pH-induced hyperpolarization in hamster eggs. Although the Na+-Ca2+ exchange system is facilitated at high pHo, the effect of this facilitation of efflux is outweighed by the inhibition of the Ca2+ pump.

Action Potentials↗

Intracellular and whole-cell recordings from zona-free hamster eggs: significance of leak impalement artifact.

Measurements have been made of membrane potential and input resistance of zona-free hamster eggs from single micro-electrode recordings. At room temperature (20-23 degrees C) the mean (+/- S.D.) values for the potential and resistance were -30 +/- 8 mV and 280 +/- 130 M omega (n = 94 eggs). At 37 degrees C the mean (+/- S.D.) values for the potential and resistance were -39 +/- 13 mV and 230 +/- 60 M omega (n = 60 eggs). The most negative potential recorded at room temperature was -51 mV in a cell which had an input resistance of 620 M omega. At 37 degrees C six eggs out of sixty had potentials more negative than -50 mV and three of these gave all-or-none action potentials in response to depolarizing current pulses. In a separate series of experiments with high resistance micro-electrodes (ca. 100 M omega) six eggs out of twenty-one had potentials more negative than -50 mV and four of these were electrically excitable. Transient potential recordings during impalement indicated that the potential was more negative than -30 mV but that the insertion of a micro-electrode produced a leak pathway with a resistance of about 10 M omega, substantially smaller than the steady-state estimates of the input resistance (see above). Whole-cell recordings with patch pipettes gave potentials in the range -30 to -80 mV and input resistances in the range 180 to 350 M omega (n = 8); four eggs gave action potentials in response to depolarizing current pulses passed through the patch pipette. It is concluded that the leak impalement artifact is so significant in micro-electrode recordings from hamster eggs that it prevents routine reliable potential measurements.

Animals↗

The effect of lanthanum, quercetin and dinitrophenol on calcium-evoked electrical responses in hamster eggs.

At room temperature micro-injections of calcium or strontium produced transient hyperpolarizations with an associated rise in input conductance. By contrast micro-injections of potassium, barium, magnesium, cobalt or lanthanum did not produce hyperpolarizations. The reversal potential for the hyperpolarizing response was about -80 mV. Some responses to calcium injections appeared to suffer from an additional transient leak conductance generated by the injected current. In these cases the recovery of the potential and the conductance to normal values was prolonged. The reversal potential of this additional leak pathway was about -10 mV. Experiments designed to investigate the role of active calcium extrusion from the cells showed that extracellular lanthanum or quercetin caused a pronounced slowing of the recovery phase of the potential and conductance response to calcium injection. The metabolic uncoupler dinitrophenol also prolonged the calcium-evoked responses. The replacement of extracellular sodium by lithium or choline produced no alteration in the time course of the calcium-evoked responses, thus suggesting that sodium-calcium exchange exerts no rate control on the recovery phase of those responses.

Animals↗

An electrophysiologic study of rabbit ciliary epithelium.

Microelectrode recordings from cells in rabbit ciliary epithelium have been made in vitro. Ionophoresis of Lucifer Yellow dye from microelectrodes during measurements of potential confirmed that the recordings were intracellular. Dye passed from the impaled cells into adjacent cells in both the nonpigmented and pigmented layers of the epithelium. Electrical coupling between epithelial cells also was observed. The mean (+/- SD) values of the potential measured across the basolateral membranes of the nonpigmented cells was -65 +/- -15 mV (n = 77); the mean value of the input resistance at this intracellular recording site was 37 +/- 28 M omega (n = 17). The membrane potential was reduced by raising the concentration of extracellular potassium but unaffected by changes in the concentrations of sodium, chloride, or bicarbonate ions. After a period of deprivation of extracellular potassium, the cells hyperpolarized without a measurable change in membrane resistance when potassium was restored to the bathing solution; this transient response to potassium was abolished by preincubation with ouabain or by bathing the epithelium in a solution lacking sodium. It was concluded that the ciliary epithelial cells are permeable to potassium but exhibit only a low permeability to sodium, chloride, or bicarbonate ions; that the cells possess an electrogenic Na/K pump; and finally, that all of the cells in the epithelium function as a syncytium.

Animals↗

Calcium action potentials in unfertilized eggs of mice and hamsters.

Measurements of membrane potential and resistance have been made in zona-free eggs of mice and hamsters. The mean +/- S.D. values for membrane potential were -91 +/- 28 mV (mouse) and -97 +/- 29 mV (hamster) and for input resistance were 430 +/- 230 M omega (mouse) and 410 +/- 150 M omega (hamster) respectively. Large fluctuations (20 mV) of membrane potential occurred apparently at random and these were accompanied by changes of membrane resistance. Depolarizing current pulses passed through the recording micro-electrode evoked action potentials in eggs of both species. The threshold for excitation was about -50 mV, the maximum rate of rise of the action potential was about 3 V.s-1 and its peak value was about +13 mV. Action potentials could be evoked in eggs bathed in sodium-free solution or in normal solution containing tetrodotoxin (3 microM). The presence of cobalt (5-20 mM), lanthanum (1 mM) or verapamil (200-400 microM) in the bathing solution suppressed the action potential. Raising the extracellular calcium concentration from 4 to 40 mM increased the peak value of the action potential by 25 mV. It is concluded that the plasma membranes of mouse and hamster eggs have voltage-dependent calcium channels.

Action Potentials↗

Calcium-evoked opening of potassium channels in hamster eggs.

Measurements of membrane potential and resistance have been made in zona-free hamster eggs. The resting potential lay in the range -9 to -100 mV and the input resistance fell in the range 14 to 440 M omega; high resting potentials were associated with large input resistances. Calcium injected ionophoretically into an egg from an intracellular micro-electrode caused a reduction of the membrane resistance. The estimated reversal potential for the calcium-evoked response was about -80 mV and its amplitude depended on the extracellular concentration of potassium but not on the chloride concentration. We conclude that membrane potassium channels open in response to a rise in the cytosolic concentration of calcium ions. Evidence is presented to suggest that micro-electrode recordings of the membrane potential and resistance of eggs suffer from an impalement leak artifact. The presence of the artifact lowers the resting potential and resistance of the cell so that intracellular calcium injection causes a hyperpolarization. We conclude that a hyperpolarizing response to calcium would be unlikely in the absence of an impalement artifact.

Animals↗

Bronchiectasis in systemic sclerosis. A study using high resolution computed tomography.

OBJECTIVE: To detect noninvasively the presence of bronchiectasis in patients with systemic sclerosis (SSc), through the use of high resolution chest computed tomography (HRCT). METHODS: Twenty two patients with SSc, of whom 13 with diffuse and 9 with limited disease, besides a complete history, physical and routine laboratory and immunologic profile, were evaluated by pulmonary function testing and HRCT. The chi square test with Yates' correction, the Fisher's exact test, the Fisher's test (F test) and the "t" test were used for statistical analysis of the results. RESULTS: Eleven patients (50.0%) had decreased carbon monoxide diffusing lung capacity (DLCO) and, out of these, four had restrictive lung disease, based on a combined decrease of forced vital capacity (FVC) and total lung capacity (TLC). Another two patients exhibited this pattern without DLCO impairment. HRCT revealed a ground glass picture in 15 patients (68.2%), fibrosis in 9 (40.9%) (of which 5 with ground glass as well), and cylindrical bronchiectasis in 13 (59.1%). Bronchiectasis was more common in diffuse than in limited SSc, and the difference approached but did not reach the level of statistical significance. On the other hand, it was not correlated with either decreased DLCO, presence of ground glass and fibrosis, or with patients' age and disease duration. CONCLUSION: Although the number of patients included in our study is relatively small, our data, for the first time in the literature, indicate a significant association between scleroderma and bronchiectasis. Bronchiectasis should be included in the list of pulmonary manifestations of SSc, and SSc in the list of conditions causing bronchiectasis.

Adult↗

Asymptomatic gastrocnemius muscle biopsy: an extremely sensitive and specific test in the pathologic confirmation of sarcoidosis presenting with hilar adenopathy.

OBJECTIVE: To evaluate asymptomatic gastrocnemius muscle biopsy as a tool in the histologic confirmation of the diagnosis of sarcoidosis. METHODS: Twenty-two patients admitted over a 2-year period to our department with bilateral hilar adenopathy and a variety of symptoms compatible with sarcoidosis were studied prospectively. Besides a complete history and physical, serum angiotensin converting enzyme (SACE) determination, pulmonary function, slit lamp eye examination, PPD skin test, gallium 67 scan and gastrocnemius muscle biopsy were performed. RESULTS: The biopsy revealed non-caseating granuloma in all patients, confirming the diagnosis of sarcoidosis. No other patient in our department received this diagnosis over the 2-year period of the study. The procedure was well tolerated by all patients and almost zero morbidity was noted. Erythema nodosum was present in 68.2% of the patients, PPD was negative in all of them, SACE was elevated in 59.1% and pulmonary function was normal in the majority. CONCLUSION: The impressive sensitivity of asymptomatic gastrocnemius muscle biopsy, its safety and ease of performance, along with the extreme rarity of muscle involvement by other granulomatous diseases included in the differential diagnosis, may render it the procedure of choice for the histologic confirmation of sarcoidosis presenting with hilar adenopathy.

Adolescent↗