Log Ca Research Articles

Ryanodine sensitizes the cardiac Ca(2+) release channel (ryanodine receptor isoform 2) to Ca(2+) activation and dissociates as the channel is closed by Ca(2+) depletion.

In single-channel recordings, the rabbit cardiac Ca(2+) release channel (RyR2) is converted to a fully open subconductance state with about 50% of full conductance by micromolar concentrations of ryanodine. At +30 mV, corresponding to a luminal to cytoplasmic cation current, the probability of opening (P(o)) of ryanodine-modified channels was only marginally altered at pCa 10 (pCa = -log(10) Ca concentration). However, at -30 mV, the P(o) was highly sensitive to Ca(2+) added to the cis (cytoplasmic) side and, at pCa 10, was reduced to less than 0.27. The EC(50) value for channel opening was about pCa 8. No significant Ca(2+) inactivation was observed for ryanodine-modified channels at either -30 mV or +30 mV. The opening of unmodified Ca(2+) channels is Ca(2+) sensitive, with an EC(50) value of about pCa 6 (two orders of magnitude less sensitive than ryanodine-modified channels) and IC(50) values of pCa 2.2 at -30 mV and 2.5 at +30 mV. Mg(2+) decreased the P(o) of ryanodine-modified channels at low Ca(2+) concentrations at both -30 and +30 mV. Caffeine, ATP, and ruthenium red were modulators of the P(o) of ryanodine-modified channels. In a [(3)H]ryanodine binding assay, [(3)H]ryanodine dissociation from the high-affinity binding site was found to be Ca(2+) sensitive, with an IC(50) of pCa 7.1. High concentrations of unlabeled ryanodine prevented [(3)H]ryanodine dissociation, but ruthenium red accelerated dissociation. These results suggest that ryanodine sensitizes Ca(2+) activation of the Ca(2+) release channel and desensitizes Ca(2+) inactivation through an allosteric interaction. [(3)H]Ryanodine dissociates from the high-affinity site when the channel is closed by removal of Ca(2+), implying that high-affinity ryanodine and Ca(2+) binding sites are linked through either short- or long-range interactions, probably involving conformational changes.

Solubility of diphenyl sulfone in organic nonelectrolyte solvents. Comparison of observed versus predicted values based upon the general solvation model

Experimental solubilities are reported for diphenyl sulfone dissolved in 8 alkane, 10 alcohol, and in aqueous solvent media at 25°C. Results of these measurements are used to test the predictive ability of the general solvation model log CA,orgsat/CA,aqsat = c + rR2 + sπ2H + aΣα2H + bΣβ2H + vVxwhere CA,orgsat and CA,aqsat refer to the solute solubility in the organic solvent and in water, respectively, R2 is the solute's excess molar refraction, Vx is the McGowan characteristic volume of the solute, π2H denotes the solute's dipolarity/ polarizability, and Σα2H and Σβ2H are the overall hydrogen-bond acidity and basicity descriptors for the solute. The remaining symbols in the above expression are known solvent coefficients, which have been determined previously through regressional analysis of published organic solvent - water partition coefficient and vapor-liquid equilibrium data. Computations show that the general solvation model predicts the solubility behavior of diphenyl sulfone in the 11 organic solvents for which predictions could be made to within an overall average absolute deviation of about ±20%. Key words: diphenyl sulfone solubilities, organic solvents, solubility predictions, general solvation model.

Solubility of diphenyl sulfone in organic nonelectrolyte solvents. Comparison of observed versus predicted values based upon the general solvation model

Experimental solubilities are reported for diphenyl sulfone dissolved in 8 alkane, 10 alcohol, and in aqueous solvent media at 25°C. Results of these measurements are used to test the predictive ability of the general solvation model log CA,orgsat/CA,aqsat = c + rR2 + sπ2H + aΣα2H + bΣβ2H + vVxwhere CA,orgsat and CA,aqsat refer to the solute solubility in the organic solvent and in water, respectively, R2 is the solute's excess molar refraction, Vx is the McGowan characteristic volume of the solute, π2H denotes the solute's dipolarity/ polarizability, and Σα2H and Σβ2H are the overall hydrogen-bond acidity and basicity descriptors for the solute. The remaining symbols in the above expression are known solvent coefficients, which have been determined previously through regressional analysis of published organic solvent - water partition coefficient and vapor-liquid equilibrium data. Computations show that the general solvation model predicts the solubility behavior of diphenyl sulfone in the 11 organic solvents for which predictions could be made to within an overall average absolute deviation of about ±20%. Key words: diphenyl sulfone solubilities, organic solvents, solubility predictions, general solvation model.

Increase in calcium responsiveness of cardiac myofilament activation in ovariectomized rats

To evaluate a possible role of ovarian sex hormones in the Ca 2+ responsiveness of cardiac myofilament activation, the relations of pCa (−log Ca 2+ molar concentration) to actomyosin adenosine triphosphatase (ATPase) activity of isolated myofibrillar preparations from 8–10 week ovariectomized (Ovx) rat hearts were compared with those from sham-operated hearts. Deficiency of ovarian sex hormones in plasma of ovariectomized rats was indirectly verified by a significant reduction in uterine weights. Body weights of the ovariectomized rats were significantly greater than those of sham-operated controls. Despite a significant increase in heart weight of 10 week ovariectomized animals, the percent of heart weight-to-body weight ratio was not different from control group. The maximum myofibrillar ATPase activity at pH 7.0 was significantly suppressed after ovariectomy in both eight and ten week groups. However, the maximum ATPase activity at pH 6.5 was significantly suppressed only in 10 week ovariectomized hearts. Surprisingly, in every condition with depressed maximum myofibrillar ATPase activity, the pCa-actomyosin ATPase relationships of ovariectomized cardiac myofilaments demonstrated a significant leftward shift in pCa 50 (−log half-maximally Ca 2+ activation) from those of sham-operated controls. There was, however, no change in the Hill-coefficient of these cardiac myofilaments after ovariectomy. Analysis of myofilament proteins using gel electrophoresis demonstrated neither change nor loss of any thin filament proteins. These results indicate a possible modulating effect of ovarian sex hormone deficiency on the Ca 2+ responsiveness of cardiac myofilament activation by induction of myofilament Ca 2+ hypersensitivity but suppression of maximum myofibrillar ATPase activity.

Radical Reactivity of Radical Ions in Solution. Radical--Radical and Radical--Substrate Coupling Mechanisms.

The linear sweep voltammetry response to competitive radical ion-substrate coupling and radical ion dimerization mechanisms was determined by digital simulation. The simulations were carried out to mimic the conditions under which experimental studies had previously shown that the radical ion-substrate coupling mechanism is the preferred reaction pathway. It was observed that in order for the dependence of the peak potential on substrate concentration (delta Ep/delta log CA) to be in the experimentally observed range (36-40 mV/decade) that the relative rate constants for radical ion substrate coupling and radical ion dimerization (ki/kii) must be greater than about 10. It is pointed out that since the reactants, the transition states and the products differ by only a single electron that these competitive reactions represent an ideal test case for the configuration mixing (CM) model. The CM model predicts an electronic reaction barrier for reaction (i) but not for reaction (ii). The difference in standard free energy changes for reactions (i) and (ii) were estimated to be of the order of 7 kcal mol-1 or greater with (ii) being energetically more favorable than (i). It is concluded that the experimental data for the relative rates of reactions (i) and (ii) do not conform to the CM model predictions in the cases discussed. ArH(.+) + ArH-->+ ArH-ArH.(i) ArH(.+) + APH .+ --> + ArH-ArH+(ii).

The Heart Rate-Corrected QT Interval of Conscious Beagle Dogs: A Formula Based on Analysis of Covariance

Three frequently used and cited formulas used to rate correct the QT interval (Bazett's, Fridericia's, and Van de Water's) were compared and ranked using a large population-based cohort of beagle dogs (99 males and 99 females). In addition, analysis of covariance was used to derive a flexible method to rate correct the QT interval for heart rate. The method is flexible in that it utilizes pretest or control data to determine the degree of correction. In addition, it can also be used to evaluate whether treatment alters the association between heart rate and QT. Specifically, pretest QT (unadjusted) and heart rate data were used to estimate coefficients in the linear regression log(QT) = α + βlog(HR). The estimated slope (β) from the pretest data was used to heart rate correct the QT interval in the formula log(QT)ca, = log(QT) − β*[log(HR − log(HRm)]. The term “log(HRm)” is included to standardize QTca to a reference value, either a fixed value or an average heart rate for the data set being analyzed. These formulas were retrospectively compared under a typical toxicity study paradigm with a class III antiarrhythmic agent (L-768,673) that selectively prolongs the QT interval by blocking the slow activating component of the delayed rectifying potassium channel (Iks). Based on their ability to dissociate the effects of heart rate on the QT interval, the formulas received the following ranking: Covariate Adjustment (preferred) = Van De Water's > Fridericia's > Bazett's (not recommended). Analysis of covariance based on pretest or control data is preferred for moderate to large studies where there are adequate data for estimation of the slope parameter β, the investigator does not have sufficient control over HR, or treatment alters the association between HR and the QT interval. Conversely, for smaller studies a fixed rate adjustment formula from the literature (such as Van de Water's or Fridericia's equations) may be preferable since the bias from using a fixed formula is likely to be smaller than the variance resulting from estimating β from a small sample.

Biometric evaluation of gastric urease activity in man.

The 14C-urea breath test is claimed to be the best test for detection of Helicobacter pylori infection. We present a procedure for estimating its cutoff value on the basis of biometric evaluation only, without involving other diagnostic methods. Cumulative gastric urease activity (CA) was determined during the first 30 min after oral administration of 14C-urea (92.5 kBq) in 56 random volunteers and 49 consecutive patients with peptic ulcer disease. The distribution of CA in random volunteers was positively skewed. Logarithmic transformation yielded two separate populations, each normally distributed. Their normal probability density functions intercepted at log cutoff value. A bimodal distribution of log CA was confirmed in patients with peptic ulcer disease before and after treatment aimed at H. pylori eradication. Cutoff values were determined for both random volunteers and patients with peptic ulcer disease. By application of the present procedure for determination of cutoff value, the 14C-urea breath test distinguishes between individuals who have an increased gastric urease activity and individuals who do not, with the smallest possible arbitrariness.

Atmospheric Concentration of Aerially Applied Fenitrothion.

The variation of fenitrothion (MEP) concentration in the atmosphere was investigated after the aerial application of MEP for the control of pine sawyer beetles in Niigata City. In the applied area, MEP in air (CA, μg/m3) was 5.2-100μg/m3 at maximal concentrations ; MEP was detected on 12d after the application. MEP was drifted to the points located 50-1000m from the applied area ; atmospheric MEP (C, μg/m3) were 0.19-1.1μg/m3 at maximal concentrations. C was mainly dependent on passing time after the application, wind direction, air temperature and the distance from the applied area. CA (n=37) was represented by multiple regression analysis as log CA=-1.007×log T+0.01290×cos θ-0.07283×υ-1+6.033×log t-6.416 (γ2=0.736) where T (h), v (m), θ and t (°C) are passing time after the application, wind speed, wind direction (0gθg180 ; θ=0 at a NW wind) and air temperature, respectively. C (n=122) was represented as log C=-0.3165×log T+0.2154×cos θ+0.6329×υ-1+3.094×log t-0.2642×log D+0.2833×CA-4.570 (γ2=0.763) where D (m) was 100 + the distance from the applied area.

Contribution of dissolved calcium and magnesium to phytoplanktonic particulate phosphorus concentration at the heads of two river reservoirs

At the heads of two river reservoirs, the Ishitegawa Dam and the Nomura Dam Reservoirs in Japan, the concentrations of phytoplanktonic particulate phosphorus (PP) were compared with those of dissolved calcium (Ca) and magnesium (Mg), using multiple regression analyses on the data taken from samples which registered more than 6.0 µg l−1 in chlorophyll a concentration. Of the 27 monthly samples, 16 from the Ishitegawa Reservoir and 17 from the Nomura Reservoir were used. A significant regression line, logPP = k1F + k2, was obtained, where k1 (> 0) and k2 were constants and F (named the Ca-Mg index) consisted of log(Ca/Mg) − 0.5 log(ca + Mg) in mol concentration in Ca and Mg, in common with the two reservoirs (r2 = 0.730 & 0.913).

Calcium ion effects on the rising phases of action potentials obtained from guinea-pig papillary muscles at different potassium concentrations

In guinea-pig papillary muscles, action potentials, rates of rise ( v ̇ max and conduction velocities were measured at various potassium concentrations. An increase in potassium reduced v ̇ max in an S-shaped relation to the membrane potential but conduction velocity was influenced differently. At 18 to 20 m m K 0 +, the rising phase often included a remainder of the fast depolarization and v ̇ max showed two peaks; the first peak could be abolished by TTX (10 −6 m), the second peak by D600 (1 μg/ml, 1 Hz). The v ̇ max (second peak) of the rising phase of the slow responses as well as overshoot and amplitude was clearly correlated ( r = 0.99) to the log of Ca 0 2+. The increase in Ca 0 2+ concentration caused an elevation of both overshoot and amplitude of 34.22 mV per decade. In contrast, the v ̇ max of the first peak was correlated to the linear Ca 0 2+ concentration. At K 0 + 20 m m increase of Ca 0 2+ led to a marked increase of the first and Na +-dependent peak of v ̇ . This v ̇ max was increased 4.23 times by a Ca 0 2+ increase from 2.5 to 10 m m. Accordingly, impaired conduction due to 20 m m K 0 + was almost normalized by 10 m m Ca 0 2+. A Ca 0 2+-increase (2.5 to 10 m m) shifted the curve of Na +-inactivation by 4.26 mV in the depolarization direction and reduced v ̇ max at normal membrane potential. The results confirm the dependence of the rising phase and the overshoot of slow responses to the log Ca 0 2+ but indicate strong and simultaneous Ca 0 2+-effects on recovery of the Na +-system which may add to or even dominate the overall changes in v ̇ max of slow responses.

Quantal release in cut muscle: Effects of limited calcium availability

The effects of altering calcium/magnesium ratios (Ca ++/Mg ++) were tested on the rat diaphragm cut muscle preparation. Decreasing Ca ++/Mg ++ did not alter MEPPs, but evoked release was significantly depressed. The decrease in quantal content (m) was a function of Ca ++/Mg ++, and a plot of log m vs. log Ca ++/Mg ++ indicated a power relationship of 3.69. Although low Ca ++/Mg ++ caused a significant reduction in the probability of release (p), the quantal distribution was still best described by binomial statistics. Mobilization measured at high frequency (150 Hz) was reduced by decreasing Ca ++/Mg ++. Verapamil decreased m and n, but did not alter mobilization or p. The highest concentration employed (300 uM) decreased MEPP frequency and produced conduction block to high frequency EPP trains. Thus it appears that altering the effective calcium concentration has different effects on transmitter release as compared to verapamil.

Transmitter release from nerve terminals undergoing suppression

Experiments aimed at investigating the mechanism behind the decline in quantal content of foreign nerve transmission in the axolotl supracoracoideus muscle were performed. The effect of K + on spontaneous transmitter release from suppressed foreign terminals was investigated after the degeneration of native terminals. All terminals studied responded with an increase in spontaneous miniature endplate potential frequency. The possibility that transmitter release from suppressed nerve terminals is less sensitive to Ca 2+ than in non-suppressed terminals was investigated directly. Quantal content of transmission from foreign terminals undergoing suppression and from foreign terminals in muscles not reinnervated by the native nerve was measured at 3 different Ca 2+ concentrations. The relationship between the log of quantal content and log Ca 2+ concentration was similar for suppressed foreign and non-suppressed foreign terminals suggesting that there is no difference in the sensitivity to Ca 2+ of the transmitter release mechanism in the two classes of terminals. Facilitation was compared for the two classes of terminals using a pair of stimuli separated by 20 msec. No significant difference was found. No difference was also found in the degree of depression of quantal content during 1 Hz stimulation for the two classes of nerve terminal. Some of these results differ considerably from those reported previously. The possibility that the lower level of spontaneous and evoked transmitter release from suppressed terminals may be due to a reduced overall number of Ca 2+ channels in the terminal membrane or a reduced availability of transmitter release sites is compatible with reduction in the size of the nerve terminal during suppression.

Calcium Concentration of ‘Spartan’ Apple in Relation to Amount of Senescent Breakdown in Individual Fruits1

Abstract The concentration of Ca in the flesh was closely related to the amount of breakdown in individual apples in 5 lots of ‘Spartan’ apple (Malus sylvestris Mill.) collected over 2 years. Correlation coefficients of 0.9 were obtained using log Ca and linear breakdown or log Ca and log breakdown. The amount of breakdown calculated for the 5 lots by the 2 equations was 100 percent at 70 ppm Ca, from 46 to 100 percent at 100 ppm Ca, from 3 to 12 percent at 150 ppm Ca and less than 2 percent at 200 ppm.

Calcium-activated tension of skinned muscle fibers of the frog. Dependence on magnesium adenosine triphosphate concentration.

The influence of MgATP on the Ga(++)-activated isometric tension of skinned frog muscle fibers was examined in solutions containing: Mg(++) = 5 mM, creatine phosphate (CP) = 14.5 mM, creatinephosphokinase (CPK) = 1 mg/ml, total EGTA = 7 mM, CaCl(2), KCl, imidazole >/= 20 mM so that ionic strength = 0.15, pH = 7.00, and MgATP = 2 mM, 0.1 mM, or 20 microM. CP and CPK were necessary for these experiments as determined experimentally by their effect on the tension-Ca(++) relation, which was saturated for CP >/= 14.5 mM. This was interpreted to mean that sufficient CP was present to effectively buffer MgATP intracellularly. Decreasing MgATP shifts the tension-pCa curve to higher pCa (-log Ca(++)) so that, for half-maximal tension: pCa(1/2) = 4.5 for MgATP = 2 mM, pCa(1/2) = 5.1 for MgATP = 0.1 mM, and pCa(1/2) = 5.8 for MgATP = 20 microM; maximum isometric tension is the same in all cases, however. If MgATP was decreased to 1 microM, tension at Ga(++) > 10(-8) M was 84% of the maximum Ca(-+)-activated tension in 2 mM MgATP and increased only slightly to 90% for pCa = 4.5. Weber (1970, In The Physiology and Biochemistry of Muscle as Food, Volume 2, E. J. Briskey, R. G. Cassens, and B. B. Marsh, University of Wisconsin Press, Madison, Wis.), using similar solutions, observed similar shifts in half-maximal calcium activation of rabbit myofibril ATPase rates. In explanation, Weber and Bremel (1971, In Contractility of Muscle Cells and Related Processes, R. J. Podolsky, editor, Prentice-Hall, Inc., Englewood Cliffs, N.J.; Bremel and Weber, 1972, Nat. New Biol., 238:97) have described a mechanism whereby, at low ATP, "rigor complexes" are formed between myosin and thin filament actin and, in turn, alter the calcium affinity of one class of the two Ca(++)-binding sites on troponin, so that the thin filament is "turned on" for contraction at lower Ca(++) levels. Tension data from skinned fibers substantially supports this hypothesis. A stability constant for CaEGTA of 2.62 x 10(10) M(-1) was determined, with the help of F. N. Briggs, in solutions similar to those used for skinned fibers and was the same for 100 and 300 mM KCl.

The effect of training and stimulus variables on the reversal-shift ontogeny

Linear functions fitted to the proportion of optional reversal-shifts as a function of log CA were used to assess the effect of stimulus and training variables on the reversal-shift ontogeny. The results were: (1) when the dimensional salience of the two sets of cues in the stimulus compound were similar, there was no significantly different effect of size, color, or form cues on the rate parameter, suggesting that the rates of mediational development for these cues are similar. Reversal-shifts were, however, more likely with the color-form compound than with the size-color compounds throughout the tested age span, indicating that some stimulus conditions are more likely than others to produce mediated processing at all age levels. (2) The facilitative effects of labelling on reversal-shifts were greatest at the younger ages and decreased systematically over age. (3) Overtraining increased reversal-shifts at most ages but whether the facilitative effect interacts with age remains moot. (4) Neither labelling nor overtraining eliminated ontogenetic differences.

Co-operative action a calcium ions in transmitter release at the neuromuscular junction.

1. The quantitative dependence of transmitter release on external calcium concentration has been studied at the frog neuromuscular junction, using intracellular recording and taking the amplitude of the end-plate potential (e.p.p.) as an index of the number of packets released.2. The relation between [Ca] and the e.p.p. is highly non-linear. The initial part of this relation on double logarithmic co-ordinates gives a straight line with a slope of nearly four (mean 3.78 +/- 0.2 S.D. in 28 experiments). Addition of a constant amount of Mg reduces the e.p.p. without altering the slope of the log e.p.p./log Ca relation.3. The slope of this logarithmic relation diminishes as [Ca] is raised towards the normal level.4. The results are explained quantitatively on the hypothesis that Ca ions combine with a specific site X on the nerve terminal forming CaX, and that the number of packets of acetylcholine released is proportional to the fourth power of [CaX].5. The analysis suggests that a co-operative action of about four calcium ions is necessary for the release of each quantal packet of transmitter by the nerve impulse.

Calcium and Bromide Contents of Natural Waters

The linear relation observed in a log Ca++ versus log Brplot for subsurface Cl- waters is attributed to ultrafiltration by shale of sea water and fresh water that have passed through sedimentary rocks since their formation. Reactions between these solutions and sedimentary minerals, particularly dolomitization, must have contributed additional Ca++ to solution.

Mental growth in mongolism.

Curves were fitted to Stanford-Binet data for 256 mongoloid patients, representing MA as a function of CA, and it was found that the use of log CA gave a better fit to the data than the use of CA itself. The Mongoloid Quotient (MQ), a measure of relative intelligence, was defined in terms of the ratio of MA to the MA estimated from the logarithmic regression equation. The change in MQ over an interval of 7 years for 101 patients with repeated measures was negligible, whereas the change in IQ was highly significant. The coefficient of stability for MQ was also somewhat higher than that for IQ.

Calcium and Bromide Contents of Natural Waters

The linear relation observed in a log Ca++ versus log Brplot for subsurface Cl- waters is attributed to ultrafiltration by shale of sea water and fresh water that have passed through sedimentary rocks since their formation. Reactions between these solutions and sedimentary minerals, particularly dolomitization, must have contributed additional Ca++ to solution.

Mongoloid MA Is Proportional to Log CA

Mongoloid MA Is Proportional to Log CA