|
Title
|
|
|
|
Dissecting out the complex -mediated phenylephrine-induced contractions of mouse aortic segments
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| L-type Ca2+ channel (VGCC) mediated Ca2+ influx in vascular smooth muscle cells (VSMC) contributes to the functional properties of large arteries in arterial stiffening and central blood pressure regulation. How this influx relates to steady-state contractions elicited by α1-adrenoreceptor stimulation and how it is modulated by small variations in resting membrane potential (Vm) of VSMC is not clear yet. Here, we show that α1-adrenoreceptor stimulation of aortic segments of C57Bl6 mice with phenylephrine (PE) causes phasic and tonic contractions. By studying the relationship between Ca2+ mobilisation and isometric tension, it was found that the phasic contraction was due to intracellular Ca2+ release and the tonic contraction determined by Ca2+ influx. The latter component involves both Ca2+ influx via VGCC and via non-selective cation channels (NSCC). Influx via VGCC occurs only within the window voltage range of the channel. Modulation of this window Ca2+ influx by small variations of the VSMC Vm causes substantial effects on the contractile performance of aortic segments. The relative contribution of VGCC and NSCC to the contraction by α1-adrenoceptor stimulation could be manipulated by increasing intracellular Ca2+ release from non-contractile sarcoplasmic reticulum Ca2+ stores. Results of this study point to a complex interactions between α1-adrenoceptor-mediated VSMC contractile performance and Ca2+ release form contractile or non-contractile Ca2+ stores with concomitant Ca2+ influx. Given the importance of VGCC and their blockers in arterial stiffening and hypertension, they further point toward an additional role of NSCC (and NSCC blockers) herein. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
PLoS ONE
| |
|
Publication
|
|
|
|
2015
| |
|
ISSN
|
|
|
|
1932-6203
| |
|
DOI
|
|
|
|
10.1371/JOURNAL.PONE.0121634
| |
|
Volume/pages
|
|
|
|
10
:3
(2015)
, 17 p.
| |
|
Article Reference
|
|
|
|
e0121634
| |
|
ISI
|
|
|
|
000353889600166
| |
|
Pubmed ID
|
|
|
|
25803863
| |
|
Medium
|
|
|
|
E-only publicatie
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|