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21. |
Late Sodium Current and Its Contribution to Action Potential Configuration in Guinea Pig Ventricular Myocytes |
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Circulation Research,
Volume 64,
Issue 2,
1989,
Page 389-397
Tatsuto Kiyosue,
Makoto Arita,
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摘要:
We used the patch clamp technique to study the nature of the late sodium current in guinea pig ventricular myocytes. In a cell attached mode of single channel recording at room temperature (22-24°C), two kinds of late (100 msec or more after beginning of the depolarizing pulse) sodium channel activities were recognized. One is isolated brief openings appearing once for about 120 depolarizations per channel (background type), while the other type is sustained openings with rapid interruptions (burst type) that occurred only once for 2,700 depolarizations per channel. The time constant obtained from the open time histogram of the burst type (1.05 msec) was about five times longer than that of background type (0.18 msec, measured at the potential 10 mV above the threshold). Magnitude of the late sodium current flowing through the entire surface of a myocyte was estimated with tetrodotoxin (60 μM), a specific inhibitor of sodium channels, in whole-cell clamp experiments. The steady tetrodotoxin-sensitive current of 12 to 50 pA was registered at -40 mV (26±14 pA, mean±SD, n=5), in good agreement with the late sodium current calculated from the single channel recording. Tetrodotoxin produced small (-10percent;) but significant decreases in the action potential duration. These results suggest the presence of a small but significant late sodium current with slow inactlvation kinetics and that this current probably plays a significant role in maintaining the action potential plateau and the duration in guinea pig ventricular myocytes.
ISSN:0009-7330
出版商:OVID
年代:1989
数据来源: OVID
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22. |
Higher Antioxidative Capacity During a Chronic Stable Heart Hypertrophy |
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Circulation Research,
Volume 64,
Issue 2,
1989,
Page 398-406
Madhu Gupta,
Pawan Singal,
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摘要:
Changes in oxygen radical mechanisms during 6-48 weeks of heart hypertrophy in rats subjected to a narrowing of the subdiaphragmic aorta were examined. During this period, hypertrophied hearts demonstrated a stable hyperfunction, as indicated by an elevated but stable left ventricular systolic pressure, dP/dt, and aortic pressure and no change in left ventricular end diastolic pressure. Experimental animals showed increased heart-to-body weight ratios; however, the conventional signs of heart failure such as increased wet-to-dry weight ratios of liver and lung, ascites, or pleural effusion were absent. Hearts were examined for superoxide dismutase, glutathlone peroxidase, and lipid peroxide activities. The superoxide dismutase activity was significantly higher in hypertrophied hearts at 6 and 12 weeks as compared with sham-operated rats (sham controls), while no difference was seen at 24 and 48 weeks due to a marked increase in the superoxide dismutase activity of sham control hearts in these age groups. During the period studied, glutathione peroxidase activity remained unchanged in controls but was significantly elevated in hypertrophied hearts. Lipid peroxide activity as indicated by the malondialdehyde content was significantly lower in hypertrophied hearts. Perfusion of isolated control and hypertrophy hearts with xanthine-xanthine oxidase, an exogenous source of oxygen radicals, resulted in contractile failure and rise in resting tension. In hypertrophied hearts, however, the contractile force was better maintained and there was a lesser rise in resting tension after exposure to xanthine-xanthine oxidase. The study suggests the development of a higher antioxidative capacity during the stable phase of hypertrophy due to a chronic pressure overload.
ISSN:0009-7330
出版商:OVID
年代:1989
数据来源: OVID
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23. |
Collagen‐Stimulated Human Platelet Aggregation Is Mediated by Endogenous Calcium‐Activated Neutral Protease |
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Circulation Research,
Volume 64,
Issue 2,
1989,
Page 407-410
Teruhiko Toyo-oka,
Wee Shin,
Yoko Okai,
Yoshiyuki Dan,
Minoru Morita,
Masahiko Lizuka,
Tsuneaki Sugimoto,
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摘要:
To clarify the physiological role of calcium-activated neutral protease (CANP) in human platelets, we loaded the platelets with a Ca2+-sensitive fluorescent dye, fura-2, and measured the degree of aggregation, cytosolic calcium ion concentration ([Ca2+]1), and proteolysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). At physiological concentration of Ca2+(1 mM) in the incubation medium, [Ca2+], was below 0.5 μM and platelet aggregation was not shown. Ionomycin (0.15 μM) or collagen (50 μg/ml), but not ADP (10 fiM), sharply enhanced the [Ca2+]1to near 1 μM and caused the aggregation. A calcium entry blocker, verapamil, completely abolished both the [Ca2+]1rise and the aggregation. NCO-700, a membrane permeable inhibitor against cysteine proteases (including CANP), dose-dependently blocked the aggregation but did not change the [Ca2+]1transient. SDS-PAGE revealed that filamin, talin, and 70 kDa protein were specifically degraded when platelets were aggregated by ionomycin or collagen and that the proteolysis was not observed when the aggregation was blocked by verapamil or NCO-700. These data provided evidence that Ca2+entry exceeding 0.5 μM is essential, but not sufficient per se, and that activation of cysteine protease, most likely CANP, is involved in the platelet aggregation by collagen or calcium ionophore.
ISSN:0009-7330
出版商:OVID
年代:1989
数据来源: OVID
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24. |
Acknowledgment to Reviewers |
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Circulation Research,
Volume 64,
Issue 2,
1989,
Page 411-414
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ISSN:0009-7330
出版商:OVID
年代:1989
数据来源: OVID
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