Multiple Factors Influence Calcium Synchronization in Arterial Vasomotion

Department of Biomedical Engineering, Florida International University, Miami, Florida, USA.
Biophysical Journal (Impact Factor: 3.97). 01/2012; 102(2):211-20. DOI: 10.1016/j.bpj.2011.12.032
Source: PubMed


The intercellular synchronization of spontaneous calcium (Ca(2+)) oscillations in individual smooth muscle cells is a prerequisite for vasomotion. A detailed mathematical model of Ca(2+) dynamics in rat mesenteric arteries shows that a number of synchronizing and desynchronizing pathways may be involved. In particular, Ca(2+)-dependent phospholipase C, the intercellular diffusion of inositol trisphosphate (IP(3), and to a lesser extent Ca(2+)), IP(3) receptors, diacylglycerol-activated nonselective cation channels, and Ca(2+)-activated chloride channels can contribute to synchronization, whereas large-conductance Ca(2+)-activated potassium channels have a desynchronizing effect. Depending on the contractile state and agonist concentrations, different pathways become predominant, and can be revealed by carefully inhibiting the oscillatory component of their total activity. The phase shift between the Ca(2+) and membrane potential oscillations can change, and thus electrical coupling through gap junctions can mediate either synchronization or desynchronization. The effect of the endothelium is highly variable because it can simultaneously enhance the intercellular coupling and affect multiple smooth muscle cell components. Here, we outline a system of increased complexity and propose potential synchronization mechanisms that need to be experimentally tested.

Download full-text


Available from: Jaimit Parikh, Oct 03, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Please cite this paper as Nagaraja S, Kapela A, Tsoukias NM. Intercellular communication in the vascular wall: a modeling perspective. Microcirculation 19: 391-402, 2012. Movement of ions (Ca2+, K+, Na+, and Cl−) and second messenger molecules like inositol 1, 4, 5-trisphosphate inside and in between different cells is the basis of many signaling mechanisms in the microcirculation. In spite of the vast experimental efforts directed toward evaluation of these fluxes, it has been a challenge to establish their roles in many essential microcirculatory phenomena. Recently, detailed theoretical models of calcium dynamics and plasma membrane electrophysiology have emerged to assist in the quantification of these intra and intercellular fluxes and enhance understanding of their physiological importance. This perspective reviews selected models relevant to estimation of such intra and intercellular ionic and second messenger fluxes and prediction of their relative significance to a variety of vascular phenomena, such as myoendothelial feedback, conducted responses, and vasomotion.
    No preview · Article · Feb 2012 · Microcirculation (New York, N.Y.: 1994)
  • [Show abstract] [Hide abstract]
    ABSTRACT: An almost sinusoidal, large amplitude ~0.1 Hz oscillation in cortical hemodynamics has been repeatedly observed in species ranging from mice to humans. However, the occurrence of 'slow sinusoidal hemodynamic oscillations' (SSHOs) in human functional magnetic resonance imaging (fMRI) studies is rarely noted or considered. As a result, little investigation into the cause of SSHOs has been undertaken, and their potential to confound fMRI analysis, as well as their possible value as a functional biomarker has been largely overlooked. Here, we report direct observation of large-amplitude, sinusoidal ~0.1 Hz hemodynamic oscillations in the cortex of an awake human undergoing surgical resection of a brain tumor. Intraoperative multispectral optical intrinsic signal imaging (MS-OISI) revealed that SSHOs were spatially localized to distinct regions of the cortex, exhibited wave-like propagation, and involved oscillations in the diameter of specific pial arterioles, confirming that the effect was not the result of systemic blood pressure oscillations. fMRI data collected from the same subject 4 days prior to surgery demonstrates that ~0.1 Hz oscillations in the BOLD signal can be detected around the same region. Intraoperative optical imaging data from a patient undergoing epilepsy surgery, in whom sinusoidal oscillations were not observed, is shown for comparison. This direct observation of the '0.1 Hz wave' in the awake human brain, using both intraoperative imaging and pre-operative fMRI, confirms that SSHOs occur in the human brain, and can be detected by fMRI. We discuss the possible physiological basis of this oscillation and its potential link to brain pathologies, highlighting its relevance to resting-state fMRI and its potential as a novel target for functional diagnosis and delineation of neurological disease.
    No preview · Article · Oct 2013 · NeuroImage
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The ability of cells to sense and respond to physical forces has been recognized for decades, but researchers are only beginning to appreciate the fundamental importance of mechanical signals in biology. At the larger scale, there has been increased interest in the collective organization of cells and their ability to produce complex, "emergent" behaviors. Often, these complex behaviors result in tissue-level control mechanisms that manifest as biological oscillators, such as observed in fireflies, heartbeats, and circadian rhythms. In many cases, these complex, collective behaviors are controlled-at least in part-by physical forces imposed on the tissue or created by the cells. Here, we use mathematical simulations to show that two complementary mechanobiological oscillators are sufficient to control fluid transport in the lymphatic system: Ca(2+)-mediated contractions can be triggered by vessel stretch, whereas nitric oxide produced in response to the resulting fluid shear stress causes the lymphatic vessel to relax locally. Our model predicts that the Ca(2+) and NO levels alternate spatiotemporally, establishing complementary feedback loops, and that the resulting phasic contractions drive lymph flow. We show that this mechanism is self-regulating and robust over a range of fluid pressure environments, allowing the lymphatic vessels to provide pumping when needed but remain open when flow can be driven by tissue pressure or gravity. Our simulations accurately reproduce the responses to pressure challenges and signaling pathway manipulations observed experimentally, providing an integrated conceptual framework for lymphatic function.
    Full-text · Article · Aug 2015 · Proceedings of the National Academy of Sciences
Show more