Regulation of Forward Angular Impulse in Tasks With Backward Translation

Studying how elite athletes satisfy multiple mechanical objectives when initiating well-practiced, goal-directed tasks provides insights into the control and dynamics of whole-body movements. This study investigated the coordination of multiple body segments and the reaction force (RF) generated during foot contact when regulating forward angular impulse in backward translating tasks. Six highly skilled divers performed inward somersaults (upward and backward jump with forward rotation) and inward timers (upward and backward jump without rotation) from a stationary platform. Sagittal plane kinematics and RFs were recorded simultaneously during the takeoff phase. Regulation of the forward angular impulse was achieved by redirecting the RF about the total body center of mass. Significantly more backward-directed RF was observed during the first and second peak horizontal RF of the inward somersaults than the inward timers. Modulation of the horizontal RF altered the RF direction about the center of mass and the lower-extremity segments. Backward leg and forward trunk orientation and a set of relatively large knee extensor and small hip flexor net joint moments were required for forward angular impulse generation. Understanding how the forward angular impulse is regulated in trained individuals provides insights for clinicians to consider when exploring interventions related to fall prevention.

Acrobatic squirrels learn to leap and land on tree branches without falling

Arboreal animals often leap through complex canopies to travel and avoid predators. Their success at making split-second, potentially life-threatening decisions of biomechanical capability depends on their skillful use of acrobatic maneuvers and learning from past efforts. Here, we found that free-ranging fox squirrels (Sciurus niger) leaping across unfamiliar, simulated branches decided where to launch by balancing a trade-off between gap distance and branch-bending compliance. Squirrels quickly learned to modify impulse generation upon repeated leaps from unfamiliar, compliant beams. A repertoire of agile landing maneuvers enabled targeted leaping without falling. Unanticipated adaptive landing and leaping “parkour” behavior revealed an innovative solution for particularly challenging leaps. Squirrels deciding and learning how to launch and land demonstrates the synergistic roles of biomechanics and cognition in robust gap-crossing strategies.

Physiological requirements for action potential conduction, sensory awareness, and motor control

Nervous system function depends on electrical and chemical signals. The nervous impulse is a fluctuation in voltage across the neuronal cell membrane, generated by ion currents through ion-selective, voltage-sensitive membrane channels. Neuronal information is encoded in the temporal pattern of such impulses propagated along the nerve fibres at speeds that may reach about 100 m/s in fibres electrically isolated by myelin. Signal transmission to other cells via synaptic contacts occurs mainly via chemical transmitters that control membrane ion channels and give rise to electrical responses in receiving cells, with plasticity in the process making the system capable of learning and memory storage. Since impulse generation as well as synaptic transmission depends on ion flux across the membrane, energy-dependent ion pumps are critical for maintaining the ion concentration gradients necessary for the nervous signals. As a consequence, the nervous system consumes a lot of energy and is sensitive to any lack of energy.

Assembly of the Cardiac Pacemaking Complex: Electrogenic Principles of Sinoatrial Node Morphogenesis

Cardiac pacemaker cells located in the sinoatrial node initiate the electrical impulses that drive rhythmic contraction of the heart. The sinoatrial node accounts for only a small proportion of the total mass of the heart yet must produce a stimulus of sufficient strength to stimulate the entire volume of downstream cardiac tissue. This requires balancing a delicate set of electrical interactions both within the sinoatrial node and with the downstream working myocardium. Understanding the fundamental features of these interactions is critical for defining vulnerabilities that arise in human arrhythmic disease and may provide insight towards the design and implementation of the next generation of potential cellular-based cardiac therapeutics. Here, we discuss physiological conditions that influence electrical impulse generation and propagation in the sinoatrial node and describe developmental events that construct the tissue-level architecture that appears necessary for sinoatrial node function.

Double Trouble of Severe Hyperkalemia: Syncope and No Significant ECG Changes

Potassium is an important ion capable to maintain intra-extracellular electric gradient. Hyperkalemia is a common and potential life-threatening electrolyte disorder in patients presenting to the emergency setting. Variations in the intra-extracellular ionic flow may alter cells functions, skeletal and smooth muscle contractility and electric activity of myocardial cells. Hyperkalemia can be difficult to diagnose clinically because symptoms may be vague. Patients may be asymptomatic or report non-specific symptoms such as generalized fatigue, weakness, paralysis or palpitations. Syncope is unusual neurological manifestation. An increase in serum potassium levels is followed by progressively severe electrophysiological derangements in cardiac impulse generation and conduction, which are reflected in the electrocardiogram (ECG).

Molecular Basis of Atrial Fibrillation Pathophysiology and Therapy

Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. There have been significant management advances over the past 2 decades, but the burden of the disease continues to increase and there is certainly plenty of room for improvement in treatment options. A potential key to therapeutic innovation is a better understanding of underlying fundamental mechanisms. This article reviews recent advances in understanding the molecular basis for AF, with a particular emphasis on relating these new insights to opportunities for clinical translation. We first review the evidence relating basic electrophysiological mechanisms to the characteristics of clinical AF. We then discuss the molecular control of factors leading to some of the principal determinants, including abnormalities in impulse conduction (such as tissue fibrosis and other extra-cardiomyocyte alterations, connexin dysregulation and Na + -channel dysfunction), electrical refractoriness, and impulse generation. We then consider the molecular drivers of AF progression, including a range of Ca 2+ -dependent intracellular processes, microRNA changes, and inflammatory signaling. The concept of key interactome-related nodal points is then evaluated, dealing with systems like those associated with CaMKII (Ca 2+ /calmodulin-dependent protein kinase-II), NLRP3 (NACHT, LRR, and PYD domains-containing protein-3), and transcription-factors like TBX5 and PitX2c. We conclude with a critical discussion of therapeutic implications, knowledge gaps and future directions, dealing with such aspects as drug repurposing, biologicals, multispecific drugs, the targeting of cardiomyocyte inflammatory signaling and potential considerations in intervening at the level of interactomes and gene-regulation. The area of molecular intervention for AF management presents exciting new opportunities, along with substantial challenges.

Synchronized cardiac impulses emerge from multi-scale, heterogeneous local calcium signals within and among cells of heart pacemaker tissue

ABSTRACTBackgroundThe current paradigm of Sinoatrial Node (SAN) impulse generation: (i) is that full-scale action potentials (APs) of a common frequency are initiated at one site and are conducted within the SAN along smooth isochrones; and (ii) does not feature fine details of Ca2+ signalling present in isolated SAN cells, in which small subcellular, subthreshold local Ca2+ releases (LCRs) self-organize to generate cell-wide APs.ObjectivesTo study subcellular Ca2+ signals within and among cells comprising the SAN tissue.MethodsWe combined immunolabeling with a novel technique to detect the occurrence of LCRs and AP-induced Ca2+ transients (APCTs) in individual pixels (chonopix) across the entire mouse SAN images.ResultsAt high magnification, Ca2+ signals appeared markedly heterogeneous in space, amplitude, frequency, and phase among cells comprising an HCN4+/CX43- cell meshwork. The signalling exhibited several distinguishable patterns of LCR/APCT interactions within and among cells. Apparently conducting rhythmic APCTs of the meshwork were transferred to a truly conducting HCN4-/CX43+ network of straited cells via narrow functional interfaces where different cell types intertwine, i.e. the SAN anatomical/functional unit. At low magnification, the earliest APCT of each cycle occurred within a small area of the HCN4 meshwork and subsequent APCT appearance throughout SAN pixels was discontinuous.ConclusionsWe have discovered a novel, microscopic Ca2+ signalling paradigm of SAN operation that has escaped detection using low-resolution, macroscopic tissue isochrones employed in prior studies: APs emerge from heterogeneous subcellular subthreshold Ca2+ signals, resembling multiscale complex processes of impulse generation within clusters of neurons in neuronal networks.Condensed abstractBy combining immunolabeling with a novel optical technique we detected markedly heterogenous Ca2+signals within and among cell clusters of an HCN4+/CX43- meshwork in mouse sinoatrial node. These Ca2+ signals self-organized and transferred, throughout the node, to projections from an HCN4-/CX43+ network connected to a highly organized, rapidly conducting part of the CX43+ network. Thus, APs emerge from heterogeneous, subthreshold Ca2+ signaling not detected in low-resolution macroscopic isochrones. Our discovery requires a fundamental paradigm shift from concentric impulse propagation initiated within a leading site, to a multiscale/complex process, resembling the emergence of organized signals from heterogeneous local signals within neuronal networks.