| Distinct localization and modulation of Cav1.2 and Cav1.3 L-type Ca2+ channels in mouse sinoatrial node. | |
| | |
MedLine Citation:
|
PMID: 23045342 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Dysregulation of L-type Ca2+ currents in sinoatrial nodal (SAN) cells causes cardiac arrhythmia. Both Cav1.2 and Cav1.3 channels mediate sinoatrial L-type currents. Whether these channels exhibit differences in modulation and localization, which could affect their contribution to pacemaking, is unknown. In this study, we characterized voltage-dependent facilitation (VDF) and subcellular localization of Cav1.2 and Cav1.3 channels in mouse SAN cells and determined how these properties of Cav1.3 affect sinoatrial pacemaking in a mathematical model. Whole-cell Ba2+ currents were recorded from SAN cells from mice carrying a point mutation that renders Cav1.2 channels relatively insensitive to dihydropyridine antagonists. The Cav1.2-mediated current was isolated in the presence of nimodipine (1 μM), which was subtracted from the total current to yield the Cav1.3 component. With strong depolarizations (+80 mV), Cav1.2 underwent significantly stronger inactivation than Cav1.3. VDF of Cav1.3 was evident during recovery from inactivation at a time when Cav1.2 remained inactivated. By immunofluorescence, Cav1.3 colocalized with ryanodine receptors in sarcomeric structures while Cav1.2 was largely restricted to the delimiting plasma membrane. Cav1.3 VDF enhanced recovery of pacemaker activity after pauses and positively regulated pacemaking during slow heartrate in a numerical model of mouse SAN automaticity including preferential coupling of Cav1.3 to ryanodine receptor-mediated Ca2+ release. We conclude that strong VDF and colocalization with ryanodine receptors in mouse SAN cells are unique properties that may underlie a specific role for Cav1.3 in opposing abnormal slowing of heart rate. |
| | |
Authors:
|
Carl Christel; Natalia Cardona; Pietro Mesirca; Stefan Herrmann; Franz Hofmann; Joerg Striessnig; Andreas Ludwig; Matteo E Mangoni; Amy Lee |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-10-8 |
Journal Detail:
|
Title: The Journal of physiology Volume: - ISSN: 1469-7793 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 2012 Oct |
Date Detail:
|
Created Date: 2012-10-9 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0266262 Medline TA: J Physiol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Iowa; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Contribution of non-endothelium-dependent substances to exercise hyperaemia: are they O2-dependent?
Next Document: Direct and GABA mediated indirect effects of nicotinic Ach receptor agonists on striatal neurones.