Abstract:
:To investigate the interaction of cytoskeleton with the receptor modulation of ionic currents, we studied the effect of muscarinic and beta-adrenergic stimulation in adult guinea-pig ventricular cardiac myocytes treated with paclitaxel and colchicine, two drugs that respectively stabilize or destabilize microtubules. We observed that the stabilization of microtubules with paclitaxel (1 microM for 1-4 h) did not markedly affect either the kinetics of I(Ca), or the stimulatory effect of isoproterenol (Iso, 1 microM); however paclitaxel significantly blunted the response to carbachol (CCh, 1 microM). In agreement with the electrophysiological measurements, Iso induced a similar enhancement of intracellular cAMP levels in both control and paclitaxel-treated cells, while the response to CCh 1 microM was significantly reduced in paclitaxel-treated cells. The reduction of muscarinic response induced by paclitaxel was also evident in atrial cells, in which the stimulation of I(KACh) by CCh 1 microM was reduced to about 10%. Compared to the muscarinic response, paclitaxel did not have significant effect on the purinergic (adenosine 1-10 microM) modulation of I(Ca). In contrast to paclitaxel, in colchicine-treated cells, I(Ca) was not enhanced by beta-adrenergic stimulation, but instead reduced by CCh, even in the absence of previous stimulation. In conclusion, our data suggest that microtubule stabilization significantly affects the muscarinic modulation of I(Ca), by interacting with the receptor or the G-protein rather than on the intracellular signaling cascade.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Malan D,Gallo MP,Bedendi I,Biasin C,Levi RC,Alloatti Gdoi
10.1016/s0022-2828(02)00312-7keywords:
subject
Has Abstractpub_date
2003-02-01 00:00:00pages
195-206issue
2eissn
0022-2828issn
1095-8584pii
S0022282802003127journal_volume
35pub_type
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.08.011
更新日期:2010-12-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1006/jmcc.1997.0484
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doi:10.1006/jmcc.1997.0630
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.07.059
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journal_title:Journal of molecular and cellular cardiology
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