Action potential responses to changes in stimulation frequency and isoproterenol in rat ventricular myocytes.
Action potential responses to changes in stimulation frequency and isoproterenol in rat ventricular myocytes.
复制标题
DOI：
10.14814/phy2.15166
复制
发表时间：
2022-01
影响因子：
2.5
通讯作者：
Lancaster MK
中科院分区：
文献类型：
--
作者：
Howlett LA;Kirton HM;Al-Owais MM;Steele D;Lancaster MK
目前对生理应激的心室肌动作电位适应性的理解一般基于使用非生理性频率和条件的方案，将频率效应与递增的肾上腺素能刺激隔离开来。为了更好地理解，在存在和不存在肾上腺素能刺激的情况下，通过生理起搏频率评估了心室动作电位。分析单独和联合效应以评估它们复制体内反应的能力。取雄性Wistar大鼠(3个月龄；N=8只)分离的心肌细胞，采用全细胞膜片钳技术，在37℃、1、2、4、6、8和10 MHz的稳态起搏条件下，记录其稳态动作电位。比较5、100、1µM异丙肾上腺素剂量前后动作电位复极至完全复极的25、50、75、90和100%(APD25-100)。重复测量方差分析发现，注射5 NM异丙肾上腺素可使APD50-90缩短6-25%(但不同剂量之间具有可比性)(p-≤(0.03))。模拟正常大鼠心率的起搏频率(6赫兹)比1赫兹起搏的APD50延长23%。模拟运动或应激的频率(10赫兹)会缩短APD90(29%)。这些结果表明，对肾上腺素能刺激的反应和超过生理静息频率的起搏抬高时，动作电位适度缩短。我们的发现表明，大鼠心脏模拟运动反应的主要基础是动作电位平台和晚期复极的变化。这项工作提供了新的动作电位参考数据，并将通过计算技术帮助模拟大鼠心脏对生理刺激的心脏反应。
Current understanding of ventricular action potential adaptation to physiological stress is generally based on protocols using non‐physiological rates and conditions isolating rate effects from escalating adrenergic stimulation. To permit refined understanding, ventricular action potentials were assessed across physiological pacing frequencies in the presence and absence of adrenergic stimuli. Isolated and combined effects were analyzed to assess their ability to replicate in‐vivo responses. Steady‐state action potentials from ventricular myocytes isolated from male Wistar rats (3 months; N = 8 animals) were recorded at 37°C with steady‐state pacing at 1, 2, 4, 6, 8 and 10 Hz using whole‐cell patch‐clamp. Action potential repolarization to 25, 50, 75, 90 and 100% of full repolarization (APD25‐100) was compared before and after 5 nM, 100 nM and 1 µM isoproterenol doses. A Repeated measures ANOVA found APD50‐90 shortened with 5 nM isoproterenol infusion by 6–25% (but comparable across doses) (p ≤ 0.03). Pacing frequencies emulating a normal rat heart rate (6 Hz) prolonged APD50 23% compared with 1 Hz pacing. Frequencies emulating exercise or stress (10 Hz) shortened APD90 (29%). These results demonstrate modest action potential shortening in response to adrenergic stimulation and elevations in pacing beyond physiological resting rates. Our findings indicate changes in action potential plateau and late repolarization predominantly underlie simulated exercise responses in the rat heart. This work provides novel action potential reference data and will help model cardiac responses to physiological stimuli in the rat heart via computational techniques.
登录
查看更多内容
影响因子：
7.3
作者：
Fujisawa, S;Ono, K;Iijima, T
通讯作者：
Iijima, T
影响因子：
20.1
作者：
LIU, DW;GINTANT, GA;ANTZELEVITCH, C
通讯作者：
ANTZELEVITCH, C
影响因子：
20.1
作者：
Fink, MA;Zakhary, DR;Bond, M
通讯作者：
Bond, M
影响因子：
4.6
作者：
Kang, C.;Badiceanu, A.;Efimov, I. R.
通讯作者：
Efimov, I. R.
影响因子：
4
作者：
Ferrara N;Komici K;Corbi G;Pagano G;Furgi G;Rengo C;Femminella GD;Leosco D;Bonaduce D
通讯作者：
Bonaduce D