Abstract
Achieving current electricity sector targets in Central Europe (Austria, Denmark, France, Germany, Poland and Switzerland) will redistribute regional benefits and burdens at sub-national ...level. Limiting emerging regional inequalities would foster the implementation success. We model one hundred scenarios of electricity generation, storage and transmission for 2035 in these countries for 650 regions and quantify associated regional impacts on system costs, employment, greenhouse gas and particulate matter emissions, and land use. We highlight tradeoffs among the scenarios that minimize system costs, maximize regional equality, and maximize renewable electricity generation. Here, we show that these three aims have vastly different implementation pathways as well as associated regional impacts and cannot be optimized simultaneously. Minimizing system costs leads to spatially-concentrated impacts. Maximizing regional equality of system costs has higher, but more evenly distributed impacts. Maximizing renewable electricity generation contributes to minimizing regional inequalities, although comes at higher costs and land use impacts.
Improving equity is an emerging priority in climate and energy strategies, but little is known how these strategies would alter inequalities. Regional inequalities such as price, employment and land ...use are especially relevant in the electricity sector, which must decarbonize first to allow other sectors to decarbonize. Here, we show that a European low-carbon electricity sector in 2035 can reduce but also sustain associated regional inequalities. Using spatially-explicit modeling for 296 sub-national regions, we demonstrate that emission cuts consistent with net-zero greenhouse gas emissions in 2050 result in continent-wide benefits by 2035 regarding electricity sector investments, employment gains, and decreased greenhouse gas and particulate matter emissions. However, the benefits risk being concentrated in affluent regions of Northern Europe, while regions of Southern and Southeastern Europe risk high vulnerabilities due to high adverse impacts and sensitivities, and low adaptive capacities. Future analysis should investigate policy mechanisms for reducing and compensating inequalities.
Electrical stimulation is the standard technique for exploring electrical behavior of heart muscle, but this approach has considerable technical limitations. Here we report expression of the ...light-activated cation channel channelrhodopsin-2 for light-induced stimulation of heart muscle in vitro and in mice. This method enabled precise localized stimulation and constant prolonged depolarization of cardiomyocytes and cardiac tissue resulting in alterations of pacemaking, Ca2+ homeostasis, electrical coupling and arrhythmogenic spontaneous extrabeats.
Cardiac defibrillation to terminate lethal ventricular arrhythmia (VA) is currently performed by applying high energy electrical shocks. In cardiac tissue, electrical shocks induce simultaneously de- ...and hyperpolarized areas and only depolarized areas are considered to be responsible for VA termination. Because electrical shocks do not allow proper control over spatial extent and level of membrane potential changes, the effects of hyperpolarization have not been explored in the intact heart. In contrast, optogenetic methods allow cell type-selective induction of de- and hyperpolarization with unprecedented temporal and spatial control. To investigate effects of cardiomyocyte hyperpolarization on VA termination, we generated a mouse line with cardiomyocyte-specific expression of the light-driven proton pump ArchT. Isolated cardiomyocytes showed light-induced outward currents and hyperpolarization. Free-running VA were evoked by electrical stimulation of explanted hearts perfused with low K
and the K
channel opener Pinacidil. Optogenetic hyperpolarization was induced by epicardial illumination, which terminated VA with an average efficacy of ∼55%. This value was significantly higher compared to control hearts without illumination or ArchT expression (
= 0.0007). Intracellular recordings with sharp electrodes within the intact heart revealed hyperpolarization and faster action potential upstroke upon illumination, which should fasten conduction. However, conduction speed was lower during illumination suggesting enhanced electrical sink by hyperpolarization underlying VA termination. Thus, selective hyperpolarization in cardiomyocytes is able to terminate VA with a completely new mechanism of increased electrical sink. These novel insights could improve our mechanistic understanding and treatment strategies of VA termination.
Optogenetic methods enable selective de- and hyperpolarization of cardiomyocytes expressing light-sensitive proteins within the myocardium. By using light, this technology provides very high spatial ...and temporal precision, which is in clear contrast to electrical stimulation. In addition, cardiomyocyte-specific expression would allow pain-free stimulation. In light of these intrinsic technical advantages, optogenetic methods provide an intriguing opportunity to understand and improve current strategies to terminate cardiac arrhythmia as well as for possible pain-free arrhythmia termination in patients in the future. In this review, we give a concise introduction to optogenetic stimulation of cardiomyocytes and the whole heart and summarize the recent progress on optogenetic defibrillation and cardioversion to terminate cardiac arrhythmia. Toward this aim, we specifically focus on the different mechanisms of optogenetic arrhythmia termination and how these might influence the prerequisites for success. Furthermore, we critically discuss the clinical perspectives and potential patient populations, which might benefit from optogenetic defibrillation devices.
Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic stimulation of skeletal muscle from transgenic mice expressing the ...light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed with 5-ms light pulses at 30 Hz, resulting in 84% of the maximal force induced by electrical stimulation. We demonstrate the utility of this approach by selectively stimulating with a light guide individual intralaryngeal muscles in explanted larynges from ChR2-transgenic mice, which enables selective opening and closing of the vocal cords. Furthermore, systemic injection of adeno-associated virus into wild-type mice provides sufficient ChR2 expression for optogenetic opening of the vocal cords. Thus, direct optogenetic stimulation of skeletal muscle generates large force and provides the distinct advantage of localized and cell-type-specific activation. This technology could be useful for therapeutic purposes, such as restoring the mobility of the vocal cords in patients suffering from laryngeal paralysis.
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•Distributional impacts assessed for decentralized renewable generation (DREG).•Large trade-offs found between cost-efficient vs. regionally equitable allocation.•Least-cost ...allocation implies concentrating DREG to few most productive sites only.•Solar PV is key for more regional equity with small trade-offs in generation costs.•Policies for cost-efficient DREG allocation risk strengthening regional disparities.
Decentralized renewable electricity generation (DREG) has been growing at an unprecedented pace, yet the appropriate spatial allocation and associated regional equity implications remain underinvestigated. In this study, we quantify the trade-offs between cost-efficient (least-cost) and regionally equitable DREG allocation in terms of electricity generation costs, investment needs, and DREG capacity requirements. Using the case of the ambitious and publicly-approved Swiss Energy Strategy 2050, we set up a bottom-up, technology-rich electricity system model EXPANSE with Modeling to Generate Alternatives at a spatial resolution of 2’258 Swiss municipalities. In order to measure regional equity implication, we adapt the concepts of the Lorenz curve and the Gini coefficient. We find a significant trade-off by 2035 in Switzerland: 50% increase in regional equity when allocating DREG to various Swiss regions on the basis of population or electricity demand leads to 18% higher electricity generation costs. Least-cost allocation implies concentrating DREG and associated investments to few most productive locations only. Solar PV is the key technology for increasing regional equity. We conclude that in countries with spatially-uneven DREG resources like Switzerland, any policies that focus on cost efficiency should anticipate regional equity implications in advance and, if desired, minimize them by promoting solar PV.
G-protein signaling pathways are central in the regulation of cardiac function in physiological and pathophysiological conditions. Their functional analysis through optogenetic techniques with ...selective expression of opsin proteins and activation by specific wavelengths allows high spatial and temporal precision. Here, we present the application of long wavelength-sensitive cone opsin (LWO) in cardiomyocytes for activation of the G
i
signaling pathway by red light. Murine embryonic stem (ES) cells expressing LWO were generated and differentiated into beating cardiomyocytes in embryoid bodies (EBs). Illumination with red light (625 nm) led to an instantaneous decrease up to complete inhibition (84–99% effectivity) of spontaneous beating, but had no effect on control EBs. By using increasing light intensities with 10 s pulses, we determined a half maximal effective light intensity of 2.4 μW/mm
2
and a maximum effect at 100 μW/mm
2
. Pre-incubation of LWO EBs with pertussis toxin completely inhibited the light effect proving the specificity for G
i
signaling. Frequency reduction was mainly due to the activation of GIRK channels because the specific channel blocker tertiapin reduced the light effect by ~80%. Compared with pharmacological stimulation of M
2
receptors with carbachol with slow kinetics (>30 s), illumination of LWO had an identical efficacy, but much faster kinetics (<1 s) in the activation and deactivation demonstrating the temporal advantage of optogenetic stimulation. Thus, LWO is an effective optogenetic tool for selective stimulation of the G
i
signaling cascade in cardiomyocytes with red light, providing high temporal precision.
Side effects on cardiac ion channels are one major reason for new drugs to fail during preclinical evaluation. Herein we propose a simple optogenetic screening tool measuring extracellular field ...potentials (FP) from paced cardiomyocytes to identify drug effects over the whole physiological heart range, which is essential given the rate-dependency of ion channel function and drug action. Human induced pluripotent stem cell-derived cardiomyocytes were transduced with an adeno-associated virus to express Channelrhodopsin2 and plated on micro-electrode arrays. Global pulsed illumination (470 nm, 1 ms, 0.9 mW/mm
) was applied at frequencies from 1 to 2.5 Hz, which evoked FP simultaneously in all cardiomyocytes. This synchronized activation allowed averaging of FP from all electrodes resulting in one robust FP signal for analysis. Field potential duration (FPD) was ~25% shorter at 2.5 Hz compared to 1 Hz. Inhibition of hERG channels prolonged FPD only at low heart rates whereas Ca
channel block shortened FPD at all heart rates. Optogenetic pacing also allowed analysis of the maximum downstroke velocity of the FP to detect drug effects on Na
channel availability. In principle, the presented method is well scalable for high content cardiac toxicity screening or personalized medicine for inherited cardiac channelopathies.
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