Gambassi G, Spurgeon H A, Ziman B D, Lakatta E G, Capogrossi M C
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Am J Physiol. 1998 Apr;274(4):H1152-62. doi: 10.1152/ajpheart.1998.274.4.H1152.
We examined the effect of alpha 1-adrenergic receptor (AR) subtypes on contraction, cytosolic Ca2+ concentration ([Ca2+]i), and cytosolic pH (pHi) of rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH indicator carboxyseminaphthorhodafluor-1. Nonselective alpha 1-AR stimulation was effected with phenylephrine plus nadolol. alpha 1-AR subtype stimulation was achieved with alpha 1-AR and chloroethylclonidine (CEC) or with alpha 1-AR and WB-4101. Cells were in bicarbonate buffer with 0.5 mM Ca2+ and were electrically stimulated at 0.5 Hz. Results show that 1) nonselective alpha 1-AR stimulation increased twitch and [Ca2+]i transient amplitudes, myofilament response to Ca2+, and pHi; 2) alpha 1-AR plus CEC increased twitch and [Ca2+]i transient amplitudes and also enhanced myofilament response to Ca2+ via cytosolic alkalinization; 3) alpha 1-AR plus WB-4101 decreased twitch and [Ca2+]i transient amplitudes and also pHi; and 4) cytosolic acidification due to alpha 1-AR plus WB-4101 was abolished by protein kinase C inhibition (staurosporine pretreatment) or downregulation (prolonged exposure to phorbol esters). In summary, the net effects of alpha 1-adrenergic stimulation on contraction, [Ca2+]i, and pHi are due to opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways.
我们研究了α1 - 肾上腺素能受体（AR）亚型对负载Ca2+指示剂indo 1或pH指示剂羧基半萘罗丹明氟-1的大鼠心室肌细胞收缩、胞质Ca2+浓度（[Ca2+]i）和胞质pH（pHi）的影响。用去氧肾上腺素加纳多洛尔进行非选择性α1 - AR刺激。用α1 - AR和氯乙可乐定（CEC）或α1 - AR和WB - 4101实现α1 - AR亚型刺激。细胞置于含0.5 mM Ca2+的碳酸氢盐缓冲液中，并以0.5 Hz进行电刺激。结果表明：1）非选择性α1 - AR刺激增加了单收缩和[Ca2+]i瞬变幅度、肌丝对Ca2+的反应以及pHi；2）α1 - AR加CEC增加了单收缩和[Ca2+]i瞬变幅度，并通过胞质碱化增强了肌丝对Ca2+的反应；3）α1 - AR加WB - 4101降低了单收缩和[Ca2+]i瞬变幅度以及pHi；4）α1 - AR加WB - 4101引起的胞质酸化通过蛋白激酶C抑制（星形孢菌素预处理）或下调（长期暴露于佛波酯）而被消除。总之，α1 - 肾上腺素能刺激对收缩、[Ca2+]i和pHi的净效应是由于相反的WB - 4101和CEC敏感的α1 - AR亚型信号通路所致。
