Dataset Information

Examining the role of mitochondria in Ca²? signaling in native vascular smooth muscle.

ABSTRACT: Mitochondrial Ca²? uptake contributes important feedback controls to limit the time course of Ca²? signals. Mitochondria regulate cytosolic [Ca²?] over an exceptional breath of concentrations (~200 nM to >10 ?M) to provide a wide dynamic range in the control of Ca²? signals. Ca²? uptake is achieved by passing the ion down the electrochemical gradient, across the inner mitochondria membrane, which itself arises from the export of protons. The proton export process is efficient and on average there are less than three protons free within the mitochondrial matrix. To study mitochondrial function, the most common approaches are to alter the proton gradient and to measure the electrochemical gradient. However, drugs which alter the mitochondrial proton gradient may have substantial off target effects that necessitate careful consideration when interpreting their effect on Ca²? signals. Measurement of the mitochondrial electrochemical gradient is most often performed using membrane potential sensitive fluorophores. However, the signals arising from these fluorophores have a complex relationship with the electrochemical gradient and are altered by changes in plasma membrane potential. Care is again needed in interpreting results. This review provides a brief description of some of the methods commonly used to alter and measure mitochondrial contribution to Ca²? signaling in native smooth muscle.

SUBMITTER: McCarron JG

PROVIDER: S-EPMC3708117 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Examining the role of mitochondria in Ca²⁺ signaling in native vascular smooth muscle.

McCarron John G JG Olson Marnie L ML Wilson Calum C Sandison Mairi E ME Chalmers Susan S

Microcirculation (New York, N.Y. : 1994) 20130501 4

Mitochondrial Ca²⁺ uptake contributes important feedback controls to limit the time course of Ca²⁺ signals. Mitochondria regulate cytosolic [Ca²⁺] over an exceptional breath of concentrations (~200 nM to >10 μM) to provide a wide dynamic range in the control of Ca²⁺ signals. Ca²⁺ uptake is achieved by passing the ion down the electrochemical gradient, across the inner mitochondria membrane, which itself arises from the export of protons. The proton export process is efficient and on average ther ...[more]

PMID: 23305516

Similar Datasets

Project description:Peroxisome proliferator activated receptor γ (PPARγ) has been reported to play a protective role in the vasculature; however, the underlying mechanisms involved are not entirely known. We previously showed that vascular smooth muscle-specific overexpression of a dominant negative human PPARγ mutation in mice (S-P467L) leads to enhanced myogenic tone and increased angiotensin-II-dependent vasoconstriction. S-P467L mice also exhibit increased arterial blood pressure. Here we tested the hypotheses that a) mesenteric smooth muscle cells isolated from S-P467L mice exhibit enhanced angiotensin-II AT1 receptor signaling, and b) the increased arterial pressure of S-P467L mice is angiotensin-II AT1 receptor dependent. Phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase (ERK1/2) was robustly increased in mesenteric artery smooth muscle cell cultures from S-P467L in response to angiotensin-II. The increase in ERK1/2 activation by angiotensin-II was blocked by losartan, a blocker of AT1 receptors. Angiotensin-II-induced ERK1/2 activation was also blocked by Tempol, a scavenger of reactive oxygen species, and correlated with increased Nox4 protein expression. To investigate whether endogenous renin-angiotensin system activity contributes to the elevated arterial pressure in S-P467L, non-transgenic and S-P467L mice were treated with the AT1 receptor blocker, losartan (30 mg/kg per day), for 14-days and arterial pressure was assessed by radiotelemetry. At baseline S-P467L mice showed a significant increase of systolic arterial pressure (142.0 ± 10.2 vs 129.1 ± 3.0 mmHg, p<0.05). Treatment with losartan lowered systolic arterial pressure in S-P467L (132.2 ± 6.9 mmHg) to a level similar to untreated non-transgenic mice. Losartan also lowered arterial pressure in non-transgenic (113.0 ± 3.9 mmHg) mice, such that there was no difference in the losartan-induced depressor response between groups (-13.53 ± 1.39 in S-P467L vs -16.16 ± 3.14 mmHg in non-transgenic). Our results suggest that interference with PPARγ in smooth muscle: a) causes enhanced angiotensin-II AT1 receptor-mediated ERK1/2 activation in resistance vessels, b) and may elevate arterial pressure through both angiotensin-II AT1 receptor-dependent and -independent mechanisms.

Dataset Information

Examining the role of mitochondria in Ca²? signaling in native vascular smooth muscle.

Publications

Examining the role of mitochondria in Ca²⁺ signaling in native vascular smooth muscle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets