Mouse Heart Anatomy, Conduction, and Micro-Structure

The mouse heart is a key model in cardiovascular research due to its genetic similarity to the human heart and rapid physiological processes. Examining its structure, conduction system, and microanatomy provides insights into cardiac function, disease mechanisms, and potential treatments.

Its anatomical organization, electrical activity, and microscopic features reveal adaptations that support its high metabolic demands and fast heart rate.

Anatomy

The mouse heart follows the fundamental vertebrate cardiac structure but has adaptations suited to its small size and high metabolic rate. Its compact organization ensures rapid circulation to meet physiological demands. Examining its chamber arrangement, valvular structures, and myocardial wall thickness provides a deeper understanding of its function.

Chamber Organization

The mouse heart consists of four chambers: two atria and two ventricles, mirroring the mammalian blueprint. The right atrium receives systemic venous blood via the superior and inferior vena cava, directing it into the right ventricle, which pumps it to the lungs through the pulmonary artery. Oxygenated blood returns to the left atrium via the pulmonary veins before entering the left ventricle, which propels it into systemic circulation.

The left ventricle is dominant in size and function due to the higher pressure required for systemic perfusion. High-resolution imaging, such as micro-CT and MRI, confirms structural similarities with larger mammals while highlighting species-specific differences in chamber volume and trabecular complexity (Damon et al., 2016, American Journal of Physiology-Heart and Circulatory Physiology).

Valvular Arrangement

Mouse heart valves ensure unidirectional blood flow, functioning similarly to human valves. The atrioventricular (AV) valves separate the atria from the ventricles, with the tricuspid on the right and the mitral on the left. These valves consist of thin, fibrous leaflets supported by chordae tendineae and papillary muscles, preventing prolapse during contraction.

The semilunar valves—pulmonary and aortic—regulate outflow from the ventricles. Mouse valves are thinner and more delicate than those in larger mammals, adapted for rapid contractile cycles. Scanning electron microscopy has revealed increased elasticity and reduced calcification susceptibility, contributing to resilience against valvular pathologies (Mekkaoui et al., 2018, Circulation Research).

Myocardial Wall Thickness

The mouse myocardium exhibits significant ventricular asymmetry, with the left ventricular wall being thicker than the right to accommodate higher systemic pressure. Histological studies indicate that the left ventricular free wall measures approximately 1.2–1.5 mm, while the right ventricular wall is thinner at 0.3–0.5 mm. The interventricular septum shares thickness characteristics with the left ventricular wall.

The myocardium is densely packed with cardiomyocytes and has a high capillary-to-myocyte ratio, ensuring efficient oxygen and nutrient delivery. Advanced imaging, such as echocardiography, has quantified myocardial thickness variations across strains, revealing genetic influences on cardiac morphology (Ho et al., 2020, Journal of Molecular and Cellular Cardiology). These adaptations support the mouse heart’s rapid contractile activity and resistance to ischemic stress.

Conduction System

The mouse heart’s conduction system sustains its rapid heart rate, typically between 500 and 700 beats per minute. Specialized cardiomyocytes generate and propagate electrical impulses, ensuring synchronized contraction.

The sinoatrial (SA) node, located in the right atrial wall, serves as the primary pacemaker. It initiates depolarization through spontaneous action potentials, driven by a high intrinsic firing rate. The mouse SA node is small but densely innervated and expresses high levels of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, particularly HCN4, which regulate pacemaker activity.

The electrical impulse spreads through the atrial myocardium to the atrioventricular (AV) node at the base of the right atrium. The AV node serves as a relay, delaying conduction to allow optimal ventricular filling. Conduction velocity through the AV node is slower due to a lower density of gap junctions, particularly connexin 43 (Cx43), which modulates electrical coupling.

From the AV node, the signal travels through the His-Purkinje system, consisting of the His bundle, bundle branches, and Purkinje fibers. The His bundle extends from the AV node into the interventricular septum, bifurcating into right and left bundle branches. These branches divide into Purkinje fibers that rapidly distribute the impulse to the ventricles. Unlike in larger mammals, where Purkinje fibers form a distinct subendocardial network, the mouse heart exhibits a more diffuse distribution. Optical mapping studies show ventricular activation occurs within 10 milliseconds, highlighting the efficiency of this system.

Heart Rate Patterns

The mouse heart beats at 500 to 700 beats per minute at rest, reflecting its high metabolic demands. Unlike larger mammals, mice exhibit pronounced heart rate variability due to heightened sympathetic activity. Even minor environmental stimuli, such as handling or temperature changes, can push heart rates beyond 800 beats per minute. This sensitivity is largely due to dominant β-adrenergic signaling, which facilitates rapid cardiac output adjustments.

Telemetry and electrocardiographic studies show murine heart rate responds significantly to pharmacological and genetic modifications. β-adrenergic agonists like isoproterenol can raise rates beyond 900 beats per minute, while β-blockers like propranolol reduce resting frequencies. Knockout models targeting autonomic receptors or ion channel regulators reveal intrinsic pacemaker adaptations affecting rate modulation. For example, mice lacking HCN4, a key ion channel governing SA node excitability, display bradycardia, underscoring the molecular determinants of baseline rhythm.

Circadian rhythms influence murine heart rate, with nocturnal elevations aligning with their active phase. Continuous telemetry recordings show a nighttime increase of 10–20%, regulated by fluctuations in parasympathetic and sympathetic balance. Vagal dominance during the light phase contributes to brief periods of bradycardia. Disruptions in circadian rhythm, whether genetic or environmental, can lead to sustained cardiac dysregulation.

Blood Supply

The mouse coronary circulation is highly specialized to sustain its rapid metabolism and continuous contractile activity. Despite its small size, the coronary vasculature is intricately branched, ensuring efficient oxygen and nutrient delivery. The left and right coronary arteries originate from the aortic sinuses and immediately bifurcate into subepicardial and intramyocardial networks. The left coronary artery gives rise to the left anterior descending and circumflex branches, perfusing the left ventricle and septum, while the right coronary artery supplies the right ventricular free wall.

Mice have a high capillary-to-myocyte ratio, facilitating rapid oxygen diffusion. Coronary flow is regulated by endothelial and metabolic factors that adjust vascular tone in response to oxygen consumption. Nitric oxide (NO) plays a dominant role in vasodilation, with endothelial nitric oxide synthase (eNOS) highly expressed in murine coronary endothelium. Genetic deletion of eNOS impairs coronary flow reserve and increases ischemic susceptibility, highlighting its role in perfusion. Adenosine-mediated vasodilation also supports coronary flow, particularly during increased workload.

Microscopic Structure

At the microscopic level, the mouse heart is optimized for rapid contraction and metabolic efficiency. Cardiomyocytes, the predominant cell type, are arranged in parallel bundles with intercalated discs that facilitate synchronized electrical transmission. These discs contain desmosomes and gap junctions, primarily composed of connexin 43 (Cx43), enabling rapid ion exchange. Murine cardiomyocytes are smaller in diameter but densely packed, enhancing oxygen diffusion. Mitochondria occupy nearly 30% of cardiomyocyte volume, reflecting reliance on oxidative phosphorylation for energy production.

The extracellular matrix (ECM) maintains myocardial integrity, primarily composed of collagen types I and III. Fibroblasts regulate ECM turnover and contribute to tissue remodeling under stress. Multiphoton microscopy studies reveal strain-dependent ECM adaptations, with some exhibiting increased collagen deposition linked to fibrosis. The capillary network is exceptionally dense, with an estimated capillary-to-cardiomyocyte ratio of nearly 1:1, ensuring efficient oxygen and metabolite exchange. This extensive vascularization is critical for sustaining myocardial function under high metabolic demand, and disruptions in capillary density are linked to impaired cardiac performance in disease models.