Physiological contractility of cardiomyocytes in the wall of mouse and rat azygos vein

Abstract

We recently demonstrated the abundant presence of cardiomyocytes in the wall of thoracic veins of adult mouse and rat. The highly differentiated morphology and myofilament protein contents of the venous cardiomyocytes suggested contractile functions. Here we further investigated the contractility of mouse and rat azygos venous rings compared with that of atrial strips and ventricular papillary muscle. 5-Bromo-4-chloro-indolyl-galactopyranoside (X-gal) staining of transgenic mouse vessels expressing lacZ under a cloned cardiac troponin T promoter demonstrated that the venous cardiomyocytes are discontinuous from atrial myocardium and aligned in the wall of thoracic veins perpendicular to the vessel axis. Histological sections displayed sarcomeric striations in the venous cardiomyocytes, which indicate an encirclement orientation of myofibrils in the vessel wall. Mechanical studies found that the rings of mouse and rat azygos vein produce strong cardiac type twitch contractions when stimulated with electrical pacing in contrast to the weak and slow smooth muscle contractions induced using 90 mM KCl. The twitch contraction and relaxation of mouse azygos veins further exhibited a cardiac type of β-adrenergic responses. Quantitative comparison showed that the contractions of venous cardiomyocytes are slightly slower than those of atrium muscle but significantly faster than those of ventricular papillary muscle. These novel findings indicate that the cardiomyocytes abundant in the wall of rodent thoracic veins possess fully differentiated cardiac muscle phenotype despite their anatomical and functional segregations from the heart.

Morpho-functional characterization of the systemic venous pole of the reptile heart

“…Propagation speed, however, also depends on the density of sodium channels which we did not assess in the anole lizard and python. Also, the myocardium of the reptile sinus venosus and atria respond similarly to adrenergic and cholinergic stimulation, as does the myocardium of the caval veins and atria of mammals 38 , 42 , 43 . The Anolis sinus venosus myocardium, however, in its entirety remains distinct from atrial myocardium by expressing Tbx18 .…”

“…In the sinus venosus of reptiles, the significance of expression of Tbx18 and absence of Tbx20 may be that the sinus venosus is poorly atrialized. In the postnatal mammalian heart, atrialized sinus myocardium, like atrial myocardium, expresses gap junction proteins 47 , cardiac troponins 38 , and is regulated by sympathetic and parasympathetic agonists 42 , 43 . Contractions of the atrialized sinus myocardium are in twitches and tetanus cannot be induced 42 .…”

“…The myocardium of the caval veins of the mammalian heart is paradoxical, because it has no documented beneficial function but nonetheless poses a risk to cardiac function by exhibiting ectopic pacemaker activity 5 , 42 . Current hypotheses on the function of the caval vein myocardium were originally formulated for the pulmonary venous myocardium; the systemic venous myocardium could function as a throttle valve inhibiting regurgitation from the right atrium to the veins, could aid right atrial filling, and could regulate systemic venous pressure and blood flow 42 , 48 . The first and second function, however, are doubtful in light of evolution because the un-remodeled sinuatrial junction of the reptile heart has a valve, which prevents atrial regurgitation and the reptilian sinus venosus appears to aid atrial filling.…”

Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review

“…The alternative splicing pattern of cardiac TnT is synchronized in developing cardiac and skeletal muscle independent of functional demands (Jin, 1996 ). It was further demonstrated that the abundant cardiomyocytes present in the walls of developing and adult rat and mouse thoracic veins exhibit patterns of cardiac TnT alternative splice forms identical to that in the heart (Kracklauer et al, 2013 ; Liu et al, 2014 ). These findings strongly support that the regulation of cardiac TnT alternative splicing during development and differentiation is under systemic control rather than directly responding to functional demands or adaptation.…”