Dual action (stimulation, inhibition) of D600 on contractility and calcium channels in guinea‐pig and cat heart cells.
Dual action (stimulation, inhibition) of D600 on contractility and calcium channels in guinea‐pig and cat heart cells.
复制标题
D600 对豚鼠和猫心脏细胞的收缩性和钙通道的双重作用（刺激、抑制）。
DOI：
10.1113/jphysiol.1989.sp017704
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
W. Trautwein
中科院分区：
文献类型：
--
作者：
T. Mcdonald;D. Pelzer;W. Trautwein
1. We examined the effects of D600 (0.2‐40 microM, generally 2 microM) on the following (i) developed tension in guinea‐pig papillary muscles, (ii) calcium current (Ica) and tension in cat ventricular muscle strands, (iii) Ica in guinea‐pig and cat ventricular myocytes, (iv) single Ca2+ channel currents carried by Ba2+ in cell‐attached membrane patches of guinea‐pig ventricular myocytes, and (v) Ba2+ currents through dihydropyridine (DHP)‐binding sites (skeletal muscle) reconstituted into single functional Ca2+ channels in lipid bilayers. 2. In 27 of 140 preparations studied, D600 elicited a transient stimulation that preceded marked inhibition. The stimulation was normally of short duration (less than 5 min) and moderate strength (less than 50% increase). 3. D600 had no effect on the unit conductance of single cardiac Ca2+ channels. Stimulation was characterized by a decrease in the number of records with no openings (blanks) and an increase in the open‐state probability of non‐blanks (longer open times, shorter closed times). Inhibition began with an increase in the number of blanks and later included a curtailment of open times and a prolongation of closed times. The net effect after 9 min D600 was a 75% reduction in average current amplitude. 4. A similar pattern of changes in channel open and closed times produced enhancement and then depression of time‐averaged open‐state probability in single reconstituted channels. 5. Single Ca2+ channel current that was stimulated by adrenaline was only slightly depressed after 2 microM‐D600 for 30 min. It may be that channel phosphorylation or Gs‐protein activation following beta‐receptor stimulation reduces channel affinity for D600. 6. Short‐lived binding of D600 to a single inhibitory site may enhance association/activation of Gs‐protein and thereby cause transient up‐regulation prior to increased drug occupancy and inhibition. Alternatively, there may be separate stimulatory and inhibitory sites. One aspect of inhibition, the increased frequency of blanks, is attributed to a stabilization of the inactivated state; the other aspect, changes in fast kinetics, seems to require a different explanation.
Bay K 8644 光学异构体对心脏钙通道电流的电压依赖性调节：对通道门控的影响。
影响因子：
20.1
作者：
Kass,RS
通讯作者：
Kass,RS
G蛋白直接调节哺乳动物心脏钙通道。
DOI：
10.1126/science.2446390
发表时间：
1987
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yatani,A;Codina,J;Imoto,Y;Reeves,JP;Birnbaumer,L;Brown,AM
通讯作者：
Brown,AM