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T Yada

Publications and source records attributed to T Yada.

At least 145 records · Page 8Linked to original sources
PubMed1990

[Usefulness for evaluation of the left ventricular disorders by apexcardiographic A-wave ratio in patients with hypertrophic cardiomyopathy].

Usefulness for evaluation of left ventricular disorders by apexcardiographic A-wave ratio was studied in 48 patients with hypertrophic cardiomyopathy. These subjects were divided into 3 groups: A-wave ratio less than or equal to 15% (group 1), 16% less than or equal to A-wave ratio less than or equal to 29% (group 2), and A-wave ratio greater than or equal to 30% (group 3). A-wave ratio was found to have a positive correlation with Time constant T (r = + 0.71), left ventricular end-diastolic pressure (r = +0.46), and left ventricular atrial kick (r = +0.55). During exercise, ejection fraction decreased significantly (p less than 0.05) in group 3 as compared to group 1. During treadmill exercise test, rise of systolic blood pressure was significantly (p less than 0.05) poor, and there was a large number of ST depression (p less than 0.05) in group 3. It was recognized by exercise thallium-201 myocardial scintigraphy, that the frequency of perfusion defect was 30% in group 3. In conclusion, high A-wave ratio may strongly suggest impaired left ventricular diastolic function, and, there was correlated to abnormal hemodynamic state during exercise. Apexcardiographic A-wave ratio proved to be useful in patients with hypertrophic cardiomyopathy. It is useful for evaluation of left ventricular disorders.

Adolescent↗
PubMed1990

[A case of silent posterior myocardial ischemia/left circumflex artery obstruction detected by prominent U-wave in right precordial leads].

A 64-year-old woman with a history of hypertension for ten years and of syncope 18 month previously visited our Division of Cardiology on 12 June, 1989. The S4 and mitral regurgitation were audible at the apex, and her electrocardiogram showed ST-depression in leads II, aVF, V5-6 and prominent U-wave (PU) in V1-3 when first seen. Then, she was thought to have a posterior myocardial ischemia. PU in V1-3 diminished whereas T-wave increased after nitrate and Ca++ blocker. Ergometer exercise ECG showed ST-depression in II, III, aVF, V4-6 and PU with decreased T-wave in V2-3 with no apparent symptoms. Simultaneously, Tl-201 myocardial imaging demonstrated a transient posterior defect. A silent posterior myocardial ischemia was, therefore, confirmed. Coronary arteriograms demonstrated subtotal obstruction of the proximal left circumflex artery, and the peripheral site was filled by collaterals from the right coronary artery. Angina-induced PU in the right precordial leads proved to be useful in detection of posterior myocardial ischemia, and this marker may also improve the possibility of detection of silent posterior ischemia.

Coronary Disease↗
PubMed1989

Galanin can inhibit insulin release by a mechanism other than membrane hyperpolarization or inhibition of adenylate cyclase.

Studies on the mode of action of galanin to inhibit insulin release in RINm5F cells have shown that basal and glyceraldehyde-stimulated release were both inhibited. Galanin was inhibitory at concentrations in the low nanomolar range. Binding studies with 125I-labeled galanin indicated that the RINm5F cells exhibit a single set of sites estimated to be of the order of 30,000 sites/cell. Displacement of 125I-galanin by galanin from the receptor sites occurred over a similar concentration range to that which inhibited insulin release. Half-displacement was achieved with 2 nM galanin. Measurements of bis-(1,3-diethylthiobarbiturate) trimethineoxonol (bis-oxonol) fluorescence showed that galanin hyperpolarized the RINm5F cell plasma membrane. Measurements of intracellular free calcium, [Ca2+]i by means of the fluorescent indicator fura-2 showed that galanin decreased [Ca2+]i. As galanin did not inhibit either basal or glyceraldehyde-stimulated insulin release in the presence of the Ca2+ channel blocker nitrendipine, the hyperpolarization and reduction of Ca2+ entry appear to be a possible explanation for the galanin effects. However, quantitatively, the effects on membrane potential and [Ca2+]i appear to be insufficient to account for the potent inhibition of insulin release. Furthermore, evidence for an additional mechanism of action was obtained from experiments with 12-O-tetradecanoylphorbol-13-acetate (TPA), a phorbol ester which stimulates insulin secretion by at least two mechanisms, one Ca2+ dependent and one Ca2+ independent. TPA-stimulated insulin release was inhibited by galanin over the same concentration range as for the inhibition of glyceraldehyde-stimulated release. Galanin inhibited TPA-stimulated release in the presence of maximally effective concentrations of nitrendipine and in the absence of extracellular Ca2+. These effects cannot be explained by hyperpolarization of the plasma membrane and consequent reduction of Ca2+ entry via the voltage-dependent Ca2+ channels. One suggested mechanism for the action of galanin is inhibition of adenylate cyclase. However, it was found that galanin inhibits insulin release even in the presence of 8-Br-cAMP, an agent which effectively bypasses adenylate cyclase. Therefore, an additional mechanism for the inhibitory effect of galanin must be present. All of the effects of galanin were sensitive to pertussis toxin. These data suggest two G-protein-dependent actions of galanin, one to hyperpolarize the plasma membrane and one at a distal point in stimulus-secretion coupling, close to the exocytotic event.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Degradation of type IX collagen by matrix metalloproteinase 3 (stromelysin) from human rheumatoid synovial cells.

The degradation of type IX collagen, a minor collagen in cartilage, was examined by treatment with three different types of matrix metalloproteinases (MMPs) purified from the culture medium of rheumatoid synovial cells. Neither MMP-1 (collagenase) nor MMP-2 (so-called 'gelatinase') could digest type IX collagen, but MMP-3 (stromelysin) readily degraded it into smaller fragments. This suggests that MMP-3 may be responsible for the pathological degradation and/or normal turnover of type IX collagen.

Animals↗
PubMed1989

Phorbol ester-stimulated insulin secretion by RINm5F insulinoma cells is linked with membrane depolarization and an increase in cytosolic free Ca2+ concentration.

In studying the regulation of insulin secretion by phorbol esters, we examined their effects on the cytosolic free Ca2+ concentration ([Ca2+]i), using the Ca2+ indicator fura-2 in the rat insulin-secreting beta-cell line RINm5F. [Ca2+]i was measured in parallel with the rate of insulin release. 50 nM 12-O-tetradecanoylphorbol-13-acetate (TPA), which may act via protein kinase C, stimulated insulin release and caused an increase in [Ca2+]i. Ca2+-free conditions eliminated the increase in [Ca2+]i and resulted in a reduced stimulation of insulin release by TPA. The Ca2+ channel blocker nitrendipine (300 nM) inhibited both the increase in [Ca2+]i and the increased rate of insulin secretion. Another phorbol ester, 4 beta-phorbol 12,13-didecanoate, which activates protein kinase C, also induced an increase in [Ca2+]i and in the rate of insulin release, while 4 alpha-phorbol 12,13-didecanoate, which fails to stimulate protein kinase C, was without effect. Further studies with bis-oxonol as an indicator of membrane potential showed that TPA depolarized the beta-cell plasma membrane. From these results, it is concluded that TPA depolarizes the plasma membrane, induces the opening of Ca2+ channels in the RINm5F beta-cell plasma membrane, increases [Ca2+]i, and results in insulin secretion. The action of TPA was next compared with that of a depolarizing concentration of KC1 (25 mM), which stimulates insulin secretion simply by opening Ca2+ channels. TPA consistently elicited less depolarization, a smaller rise of [Ca2+]i, but a greater release of insulin than KC1. Therefore an additional action of TPA is suggested, which potentiates the action of the elevated [Ca2+]i on insulin secretion.

Adenoma, Islet Cell↗
PubMed1989

Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line.

A human intestinal epithelial cell line (Intestine 407) is known to retain receptors for intestinal secretagogues such as acetylcholine (ACh), histamine, serotonin (5-HT) and vasoactive intestinal peptide (VIP). The cells were also found to possess separate receptors for secretin and ATP, the stimulation of which elicited transient hyperpolarizations coupled to decreased membrane resistances. These responses were reversed in polarity at the K+ equilibrium potential. The hyperpolarizing responses to six agonists were reversibly inhibited by quinine or quinidine. By means of Ca2(+)-selective microelectrodes, increases in the cytosolic free Ca2+ concentration were observed in response to individual secretagogues. The time course of Ca2+ responses coincided with that of hyperpolarizing responses. The responses to ACh and 5-HT were abolished by a reduction in the extracellular Ca2+ concentration down to pCa 7 or by application of Co2+. Thus, in Intestine 407 cells, not only the intestinal secretagogues, which are believed to act via increased cytosolic Ca2+ (ACh, 5-HT and histamine), but also those which elevate cyclic AMP (VIP, secretin and ATP) induce increases in cytosolic Ca2+, thereby activating the K+ conductance. It is likely that the origin of increased cytosolic Ca2+ is mainly extracellular for ACh- and 5-HT-induced responses, whereas histamine, VIP, secretin and ATP mobilize Ca2+ from the internal compartment.

Calcium↗
PubMed1989

Spontaneous and secretagogue-induced changes in cytosolic free Ca concentration measured by microfluorimetry with fura-2 on single bovine adrenal chromaffin cells.

The concentration of cytosolic Ca2+ ([Ca]in) was examined in single bovine adrenal chromaffin cells by monitoring fura-2 fluorescence with microspectrofluorimetry. To see the correlation between [Ca]in and secretion, we also measured the rates of catecholamine (CA) secretion and 45Ca efflux from populations of cells. [Ca]in was constant in the majority of single cells, but the small oscillatory changes in [Ca]in were observed in a population of cells. These spontaneous Ca oscillations, when observed, disappeared either after removal of extracellular Ca2+ or by addition of D-600 or Mn2+, but still persisted in the presence of tetrodotoxin (TTX) or after removal of extracellular Na+. In the silent cells the Ca fluctuations were often induced by Bay-K-8644. The characteristics of Bay-K-8644-induced Ca fluctuations were very similar to those of spontaneous ones. Low concentrations of nicotine (1 microM), acetylcholine (ACh; 1-2 microM), or KCl (12.5 mM) often induced oscillations riding on a steady rise in [Ca]in. These changes were rapidly suppressed by removal of either extracellular Ca2+ or Na+, or by addition of either D-600 (methoxyverapamil) or TTX. A low concentration of ACh (1 microM) or KCl (12.5 mM) also increased the rate of 45Ca efflux, but substantial secretion was not detected. On the other hand, the sustained rise in [Ca]in was evoked by 0.1 mM ACh, 20 microM nicotine, or 30 mM KCl, which was suppressed by removal of extracellular Ca2+, but was little affected by TTX. A sustained increase in 45Ca efflux upon exposure to ACh was observed, possibly reflecting the sustained rise in [Ca]in. ACh also stimulated CA secretion, which was faded out during the prolonged application. Veratridine, a Na channel activator, caused repetitive sequence of Ca transients followed by a sustained rise in [Ca]in. These results, together with the previous electrophysiological findings, suggest that: (1) the spontaneous Ca fluctuations are closely associated with occurrence of spontaneous Ca2+ and Na+ action potentials; (2) the rise in [Ca]in induced by a low concentration of nicotinic agonists of KCl is mediated by Na+ action potentials as well as gradual membrane depolarizations; (3) the oscillatory changes subsequent to a rise in [Ca]in reflect fluctuations in Ca2+ influx through the Ca2+ channels; (4) the critical [Ca]in needs to be attained before the CA secretion takes place.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Assessments of left ventricular function during exercise in patients with dilated cardiomyopathy: comparison with ischemic cardiomyopathy.

Responses to supine bicycle ergometer exercise were assessed in a study population consisting of 26 patients with dilated cardiomyopathy (DCM) and 23 patients with ischemic cardiomyopathy (ICM). Left ventricular ejection fraction (LVEF) and regional wall motion were analyzed at rest and during supine bicycle ergometer exercise with radionuclide ventriculography. Although the same degree of LVEF between DCM (23 +/- 8%) and ICM (26 +/- 4%) occurred at rest, the left ventricular regional wall motion abnormality was more prominent in DCM. LVEF during the peak exercise stage in DCM was almost unchanged (24 +/- 8%), but in ICM it decreased significantly (22 +/- 5%). Exercise-induced regional wall motion abnormalities were detected in nine patients (35%) in DCM and 13 patients (57%) in ICM. Although patients with DCM are believed to have diffuse hypokinesis of the left ventricle, severe regional wall motion abnormalities (akinesis or dyskinesis) were frequently observed. During the follow-up period of up to six years, eight patients with DCM died of congestive heart failure. In eight patients with DCM who showed decreased LVEF during exercise, five patients died. However, only three of 18 patients without decreased LVEF during exercise died. Exercise-induced left ventricular dysfunction in DCM seems to be a poor prognostic sign.

Adult↗
PubMed1988

Mobilization of Ca2+ from intracellular stores of pancreatic beta-cells by the calcium store blocker TMB-8.

TMB-8 has been used experimentally in many cell types, including endocrine cells, because of its ability to block the efflux of Ca2+ from intracellular stores without affecting influx. Unexpectedly, TMB-8 potentiates stimulated insulin release from pancreatic islets, a process believed to be dependent on the level of cytosolic Ca2+. In the present study, while having no effect on basal insulin release (in the presence of 2.8 mM glucose), TMB-8 (10, 30, and 100 microM) caused a concentration-dependent increase in 45Ca2+ efflux from 45Ca2+-preloaded islets. TMB-8 (100 microM) stimulated 45Ca2+ efflux even in the absence of extracellular Ca2+. In the presence of 5.6 mM glucose, TMB-8 (30 and 100 microM) potentiated insulin release and again increased 45Ca2+ efflux in a concentration-dependent manner. Similarly, insulin release stimulated by isobutylmethylxanthine (IBMX) was potentiated significantly, and IBMX-stimulated 45Ca2+ efflux was increased by the simultaneous introduction of 30 microM TMB-8. Thus, in pancreatic islets, TMB-8 appears to mobilize Ca2+ from intracellular stores, rather than inhibit the efflux as has been commonly accepted. In further studies, using insulin-secreting beta-cells of the RINm5F cell line, TMB-8 was shown to increase the cytosolic Ca2+ concentration in the presence and absence of extracellular Ca2+. This confirmed that mobilization of intracellular Ca2+ was occurring in the pancreatic beta-cell in response to TMB-8. Furthermore, a rise in cytosolic Ca2+ of not more than 10 nM (as induced with KCl) was found to mimick the effect of TMB-8 in conjunction with IBMX. No additional effect of TMB-8 to alter Ca2+ handling at the plasma membrane was found when 45Ca2+ uptake experiments were performed. Therefore, the paradoxical mobilization of beta-cell Ca2+ by TMB-8 appears to be a sufficient explanation for its potentiating effect on the rate of insulin secretion.

Animals↗
PubMed1988

Fluoroaluminates stimulate histamine secretion in the digitonin-permeabilized rat mast cells.

The combination of NaF and AlCl3 stimulated histamine secretion from digitonin-permeabilized rat mast cells only in the presence of trace amount of Ca2+. When NaF plus AlCl3 were added together with a maximal dose of guanosine-5'-[gamma-thio]triphosphate (GTP gamma S), the combined effect was less than additive. The results suggest that the secretory effect of fluoroaluminates is, at least partially, mediated by GTP-binding protein, which is previously found to be activated by GTP gamma S.

Aluminum↗
PubMed1988

[Graft patency and myocardial viability after aorto-coronary bypass surgery evaluated by exercise 201T1 myocardial SPECT].

To evaluate graft patency and myocardial viability after aorto-coronary (AC) bypass surgery, 58 patients (29 with old myocardial infarction and 29 with effort angina) underwent symptom-limited exercise 201T1 myocardial SPECT using a bicycle ergometer before and after surgery. The results were as follows: 1. The overall angiographic graft patency was 87% (97 of 112 grafts). 2. According to the stress SPECT images, graft patencies were 98% for areas with postoperative improvement by 201T1 uptakes, 79% for areas with unchanged patterns, and 53% for areas with worsened patterns. In spite of patent grafts, among cases with worsened 201T1 uptakes the etiologies included perioperative infarction, anastomotic strictures, and poor run-off distal to the anastomoses. 3. Following patency of grafts, postoperative normalized perfusion patterns were observed in 69% (27 of 39 segments) of segments with persistent preoperative low uptakes and 25% (4 of 16 segments) of segments with persistent preoperative defects. Thus, exercise 201T1 myocardial SPECT proved a useful diagnostic means of assessing graft patency and effectiveness. However, after AC bypass surgery, 25% of the regions which had persistent defects before surgery exhibited normal perfusion patterns. These findings suggest that persistent defects may represent hypoperfusion of viable myocardium, and that we should carefully diagnose myocardial scars.

Adult↗
PubMed1987

Evidence for the involvement of calmodulin in the operation of Ca-activated K channels in mouse fibroblasts.

The oscillation of membrane potential in fibroblastic L cells is known to result from periodic stimulation of Ca2+-activated K+ channels due to the oscillatory increase in the intracellular Ca2+ concentration. These repeated hyperpolarizations were inhibited by putative calmodulin antagonists, trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and promethazine (PMZ), and the concentrations required for half-maximal inhibition were 25, 30 and 300 microM, respectively. These doses were lower than those for reducing the membrane resistance due to nonspecific cell damages. Another calmodulin antagonist, chlorpromazine (CPZ), was also effective, but CPZ-sulfoxide was not. Intracellular pressure injections of calmodulin-interacting divalent cations, Ca2+, Sr2+, Mn2+ and Ni2+, elicited slow hyperpolarizations, whereas Mg2+ and Ba2+, which are known to be essentially inert for calmodulin, failed to evoke any responses. The injection of purified calmodulin also brought about a similar hyperpolarization. Quinine, an inhibitor of Ca2+-activated K+ channels, abolished both Ca2+- and calmodulin-induced hyperpolarizations. TFP prevented Ca2+-induced hyperpolarizations. The TFP effect was partially reversed by the calmodulin injection. It is concluded that calmodulin is involved in the operation of Ca2+-activated K+ channels in fibroblasts.

Animals↗
PubMed1987

[Acute right ventricular infarction: assessment with radionuclide ventriculography].

The clinical significance of right ventricular (RV) infarction has been neglected compared with left ventricular infarction. In recent years, however, the clinical importance of RV function in the treatment of myocardial infarction has been well recognized. We performed prospective radionuclide studies to assess the incidence and prognosis of RV infarction in 50 cases of initial acute myocardial infarction (25 cases of anterior and 25 of inferior infarction). Radionuclide ventriculography was performed within the first two days after onset of symptoms, and repeated one-two weeks and one month after the attack, respectively. RV infarction was diagnosed by the presence of severe RV regional wall motion abnormalities and positive signs of at least one of the following diagnostic signs: ST elevation at V4R in the ECG, positive 99m-technetium pyrophosphate myocardial scintigram at the RV free wall, and positive right heart catheterization findings. Results were as follows: 1. RV infarction was documented in 15 of 25 cases with inferior infarction, but there were no cases in anterior infarction. 2. There were no remarkable changes of RV ejection fraction (EF) in anterior myocardial infarction during one month (41% +/- 8% in acute phase and 43 +/- 8% in four weeks later). However, RVEF was markedly improved from 34 +/- 11% during first two days, to 38 +/- 7% during one-two weeks, and 39 +/- 8% four weeks after the attack, in cases of inferior infarction with RV infarction. Without RV infarction, RVEF in cases of inferior infarction did not show improvement. 3. In 11 of 15 cases with RV infarction, RV regional wall motion abnormalities improved to the normal range, which seemed to contribute to the improvement of RVEF. 4. Hemodynamic findings with Swan-Ganz catheters showed typical findings compatible with RV infarction only in seven of 13 cases with RV infarction. Thus this finding implies that RV failure did not always accompany RV infarction. 5. Coronary arteriography revealed that right coronary arterial lesions proximal to the RV branch were documented in all 10 cases with RV infarction who had coronary arteriography. RV infarction, caused by deranged coronary blood flow at the RV branch of the right coronary artery, showed marked improvement of RVEF during four weeks after the attack in prospective radionuclide studies. This finding was not seen in left ventricular infarction. The pathophysiological mechanism of improvement of RVEF in RV infarction would be the difference of its coronary circulation compared with that of the left ventricle.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Catheterization↗
PubMed1987

[Stress Tl-201 myocardial single photon emission computed tomography in diagnosing ischemic heart disease: its value and limitations].

The value and limitations of stress 201T1 myocardial single photon emission computed tomography (SPECT) for diagnosing ischemic heart disease (IHD) was studied. Using a dual-head rotating gamma camera system, stress SPECT and conventional planar imaging were performed for 138 patients while they were examined by symptom-limited graded bicycle ergometer exercise. All patients underwent selective coronary arteriography and left ventriculography, and 93 had myocardial infarction (MI), 30 had effort angina (EA) and 15 were normal (control). Sensitivities for detecting IHD (SPECT: planar = 96%: 89%, p less than 0.01), individual coronary arterial lesions (left anterior descending artery = LAD, 84%: 68%, p less than 0.005; left circumflex artery = LCX, 60%: 47%, NS; right coronary artery = RCA, 88%: 69%, p less than 0.01), multivessel disease (= LAD + LCX and/or RCA, 53%: 31%, p less than 0.025), and three vessel disease (60%: 13%, p less than 0.005) were significantly higher by SPECT than by planar imaging. In addition, detection of ventricular aneurysms by SPECT was possible with a reasonably high sensitivity (94%) and specificity (84%). Signs of aneurysm included 1) an extensive anterior permanent defect, 2) a large left ventricular cavity, and 3) widening of the angle composed by the septal and lateral walls toward the apex in transaxial images. Sensitivity for detecting IHD was significantly lower in patients without MI (i.e., EA) than in patients with MI (MI: EA = 100%: 83%, p less than 0.005). Sensitivity for detecting individual coronary arterial lesions was lower in the absence than in the presence of MI (LAD; 77%: 87%, LCX; 38%: 68%, RCA; 71%: 90%, respectively), with multivessel disease than with single vessel disease, and with mild than with severe grade of stenosis. Sensitivity for detecting multivessel disease was lower in patients without MI than in those with MI (31%: 61%, respectively), and in anterior MI than in posteroinferior MI, or both MIs (36%: 69%: 100%, respectively). Stress-induced ischemia of infarcted area (anterior MI, 36%; posteroinferior MI, 24%) and ventricular aneurysm (anterior MI, 21%; posteroinferior MI, 0) masked other coronary arterial stenoses in patients with previous MI. We concluded that stress 201T1 myocardial SPECT was a useful non-invasive technique for detecting IHD and individual coronary arterial lesions, multivessel disease (especially posteroinferior MI and anterior + posteroinferior MI), three vessel disease and ventricular aneurysms. However, there were limitations in detecting multivessel disease in patients with anterior MI and EA.

Coronary Disease↗
PubMed1987

[Myocardial ischemia with negative stress electrocardiography: evaluation by stress RI studies].

Patients with negative stress electrocardiography (ECG) (no ST segment depression) were re-evaluated by means of stress RI studies including 201T1 single photon emission computed tomography (SPECT) and 99mTc-RBCs radionuclide ventriculography (RNV). Four hundred seven patients, including 303 with old myocardial infarction (OMI; SPECT: 188, RNV: 115) and 104 with effort angina (EA; SPECT: 58, RNV: 46), all of whom underwent left ventriculography and coronary arteriography, were re-evaluated by symptom-limited graded bicycle ergometer exercise RI testing. The results were as follows: 1. Among those with negative stress ECG (53% of OMI and 31% of EA), 54% and 73% of OMI and EA, respectively, had positive SPECT. 2. Among those with negative stress ECG (56% of OMI and 39% of EA), 70% and 39% of OMI and EA, respectively, had positive delta EF (poor increase in ejection fraction: delta EF less than 5%) and, 41% and 28% of OMI and EA had deteriorated regional wall motion. 3. Those with OMI and negative ECG showed no correlations with the numbers of diseased vessels, infarcted sites, or ischemic areas. In conclusion, RI testing appears to be a significantly more sensitive means of detecting stress-induced ischemia, compared to stress ECG.

Adult↗
PubMed1986

Synchronous oscillation of the cytoplasmic Ca2+ concentration and membrane potential in cultured epithelial cells (Intestine 407).

Cultured epithelial Intestine 407 cells exhibit regular oscillations of the membrane potential with repeated hyperpolarizations. These hyperpolarizations were inhibited not only by K+ channel blockers (tetraethylammonium and nonyltriethylammonium) but also by inhibitors of the Ca2+-activated K+ channel (quinine and quinidine). Using Ca2+-selective microelectrodes, cyclic increases in the cytosolic free Ca2+ concentration of more than 1 X 10(-6) M were found to coincide with the cyclic membrane hyperpolarizations. Thus, it appears that the potential oscillation is brought about by the oscillation of the intracellular free Ca2+ level which induces periodic activation of the Ca2+-dependent K+ channels. Neither the deprivation of extracellular Ca2+ nor the application of Ca2+ channel blockers (Co2+ and Ni2+) abolished the potential oscillation. Mitochondrial inhibitors (KCN, NaN3, antimycin A, FCCP and dinitrophenol) inhibited the potential oscillation, whereas glycolytic inhibitors (iodoacetic acid and NaF) had no effects. Caffeine and oxalate, which affect the microsomal Ca2+ transport, failed to exert any effect upon the potential oscillation. It is concluded that the cytosolic Ca2+ oscillation results from cyclic releases of Ca2+ from the intracellular storage site, which depends upon mitochondrial activities.

Animals↗