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29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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Cav1.2 L-type Ca2+ channels control release of Ca2+ sparks in arterial smooth muscle

Cav1.2-Kanäle regulieren die Freisetzung von Ca2+-Sparks im arteriellen Gefäßmuskel

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  • K. Essin - Franz Volhard Klinik am Max Delbrück Center für Molekulare Medizin Berlin
  • F. Luft - Franz Volhard Klinik am Max Delbrück Center für Molekulare Medizin Berlin
  • S. Moosmang - Institut für Pharmakologie und Toxikologie TU München München
  • A. Welling - Institut für Pharmakologie und Toxikologie TU München München
  • F. Hofmann - Institut für Pharmakologie und Toxikologie TU München München
  • M. Gollasch - Charité- Campus Virchow-Klinikum Humboldt-Universität zu Berlin (Berlin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP36

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch036.shtml

Published: August 8, 2006

© 2006 Essin et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Ca2+ sparks activate BK channels and thus regulate vascular tone, a major determinant of blood pressure. Recent data suggest that this signaling pathway may play an important role in systemic hypertension. In arterial smooth muscle cells (SMC), Ca2+ sparks are released by opening ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR). They stimulate nearby large-conductance Ca2+ activated K+ (BK) channels, causing spontaneous transient outward currents (STOCs) that hyperpolarize the membrane potential, close L-type Cav1.2 channels and oppose myogenic vasoconstriction. Using smooth muscle-specific inactivation of the Cav1.2 channel gene in mice (SMAKO), we here demonstrate that: (i) Genetic inactivation of Cav1.2 channels substantially reduces the frequency and amplitude of Ca2+ sparks, (ii) these effects are associated with lower global cytosolic Ca2+ levels and reduced SR Ca2+ load and (iii) are completely reversed by elevating cytosolic Ca2+. Thus, Cav1.2 channels activate RyRs to release Ca2+ sparks through control of the global cytosolic [Ca2+]. This coupling process differs substantially from sarcomeric muscle, where the intimate association between the trigger Cav1.2 channel and target RyR is crucial for the release process of Ca2+ sparks.