Effect of sinus node on spontaneous release of natriuretic peptide in isolated atria

Experiments were conducted to examine the release of atrial natriuretic peptide (ANP) in an isolated atrium in the presence and absence of sinus node tissue. The first series of experiments were conducted with the aid of a metabolic chamber to examine the spontaneous release of ANP by the right atrium with and without the sinus node region. The left atrium was also studied. The right atrium with the sinus node, quiescent right atrium without the sinus node, and the left atrium were incubated at 35 degrees C in 10 mL of oxygenated Tyrode's solution. After 40 min of equilibration, the incubation medium was removed at 10-min intervals for the determination of immunoreactive ANP concentration. The right atria with the sinus node released the highest amount of ANP into the incubation medium (32.2 +/- 2.7 pg.min-1.mg-1), compared with quiescent right atria (20.9 +/- 3.7 pg.min-1.mg-1). The left atria released the least amount of ANP into the incubation medium (9.9 +/- 1.5 pg.min-1.mg-1) when compared with the quiescent right atria and the right atria. In the second series of experiments, the right atrium was divided into the sinus node region and the quiescent right atrium, and these tissues were studied in paired fashion with a modified Langendorff preparation. The right atrium without the sinus node and sinus node region were perfused with Tyrode's solution, equilibrated with 95% O2 and 5% CO2 at 37 degrees C with a constant flow of 0.5 mL/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

IP3 type 1 receptors in the heart: their predominance in atrial walls with ganglion cells

Previously we have shown that inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are abundantly expressed in the atria of rat hearts. Since arrangement of atria is very heterogeneous, in this work we focused on the precise localization of IP3 receptors in the left atrium, where the gene expression of the type 1 IP3R was the highest. The mRNA levels of the IP3 type 1 receptors in the left atrium, left ventricle and myocytes were determined using real-time polymerase chain reaction and Taqman probe. For precise localization, immunohistochemistry with the antibody against type 1 IP3Rs was performed. The mRNA of type 1 IP3 receptor was more than three times higher in the left atrium than in the left ventricle, as determined by real-time PCR. Expression of the type 1 IP3 receptor mRNA was higher in the atria, especially in parts containing cardiac ganglion cells. The atrial auricles, which are particularly free of ganglion cells, and the ventricles (wall of the right and left ventricle and ventricular septum) contained four to five times less IP3 receptors than atrial samples with ganglia. IP3R type 1 immunoreactivity detected by a confocal microscope attributed the most condensed signal on ganglionic cells, although light immunoreactivity was also seen in cardiomyocytes. These results show that type 1IP3 receptors predominate in intrinsic neuronal ganglia of cardiac atria.     

Effects of hyperthyroidism on delayed rectifier K+ currents in left and right murine atria

Hyperthyroidism has been associated with atrial fibrillation (AF); however, hyperthyroidism-induced ion channel changes that may predispose to AF have not been fully elucidated. To understand the electrophysiological changes that occur in left and right atria with hyperthyroidism, the patch-clamp technique was used to compare action potential duration (APD) and whole cell currents in myocytes from left and right atria from both control and hyperthyroid mice. Additionally, RNase protection assays and immunoblotting were performed to evaluate the mRNA and protein expression levels of K(+) channel alpha-subunits in left and right atria. The results showed that 1) in control mice, the APD was shorter and the ultra-rapid delayed rectifier K(+) conductance (I(Kur)) and the sustained delayed rectifier K(+) conductance (I(ss)) were larger in the left than in the right atrium; also, mRNA and protein expression levels of Kv1.5 and Kv2.1 were higher in the left atrium; 2) in hyperthyroid mice, the APD was shortened and I(Kur) and I(ss) were increased in both left and right atrial myocytes, and the protein expression levels of Kv1.5 and Kv2.1 were increased significantly in both atria; and 3) the influence of hyperthyroidism on APD and delayed rectifier K(+) currents was more prominent in right than in left atrium, which minimized the interatrial APD difference. In conclusion, hyperthyroidism resulted in more significant APD shortening and greater delayed rectifier K(+) current increases in the right vs. the left atrium, which can contribute to the propensity for atrial arrhythmia in hyperthyroid heart.     

Alterations in atrial and plasma atrial natriuretic factor (ANF) content during development of hypoxia-induced pulmonary hypertension in the rat

Distension of the atrial wall has been proposed as a signal for the increased release of atrial natriuretic factor (ANF) from atrial myocytes in response to perceived volume overload. To determine whether pressure changes resulting from hypertension in the pulmonary circulation may stimulate release of ANF, rats were exposed to chronic hypobaric hypoxia for 3 or 21 days and the ANF concentration in the atria and plasma were determined by specific radioimmunoassay. Exposure to chronic hypoxia resulted in significant increases in hematocrit at both 3 (p less than 0.025) and 21 days (p less than 0.005) and in the development of right ventricular hypertrophy (RVH) expressed as the ratio of the weight of the right ventricle to the weight of the left ventricle and septum (RV/LV+S) at both 3 (RV/LV+S = 0.278 +/- 0.005) and 21 days (RV/LV+S = 0.536 +/- 0.021). After 21 days, left atrial (LA) ANF content was significantly increased in hypoxic rats compared to controls (508 +/- 70 ng/mg tissue vs 302 +/- 37 ng/mg), while right atrial (RA) ANF content was significantly reduced (440 +/- 45 vs 601 +/- 58 ng/mg). At this time, plasma ANF concentration was significantly elevated compared to controls (238 +/- 107 pg/ml vs 101 +/- 10 pg/ml). These results suggest that the development of pulmonary hypertension following chronic hypobaric exposure induces altered atrial ANF content and increased plasma ANF concentration as a result of altered distension of the atrial wall.     

The slow force response to stretch in atrial and ventricular myocardium from human heart: functional relevance and subcellular mechanisms

Mechanical load is an important regulator of cardiac force. Stretching human atrial and ventricular trabeculae elicited a biphasic force increase: an immediate increase (Frank-Starling mechanism) followed by a further slow increase (slow force response, SFR). In ventricle, the SFR was unaffected by AT- and ET-receptor antagonism, by inhibition of protein-kinase-C, PI-3-kinase, and NO-synthase, but attenuated by inhibition of Na+/H+- (NHE) and Na+/Ca2+ exchange (NCX). In atrium, however, neither NHE- nor NCX-inhibition affected the SFR. Stretch elicited a large NHE-dependent [Na+]i increase in ventricle but only a small, NHE-independent [Na+]i increase in atrium. Stretch-activated non-selective cation channels contributed to basal force development in atrium but not ventricle and were not involved in the SFR in either tissue. Interestingly, inhibition of AT receptors or pre-application of angiotensin II or endothelin-1 reduced the atrial SFR. Furthermore, stretch increased phosphorylation of atrial myosin light chain 2 (MLC2) and inhibition of myosin light chain kinase (MLCK) attenuated the SFR in atrium and ventricle. Thus, in human heart both atrial and ventricular myocardium exhibit a stretch-dependent SFR that might serve to adjust cardiac output to increased workload. In ventricle, there is a robust NHE-dependent (but angiotensin II- and endothelin-1-independent) [Na+]i increase that is translated into a [Ca2+]i and force increase via NCX. In atrium, on the other hand, there is an angiotensin II- and endothelin-dependent (but NHE- and NCX-independent) force increase. Increased myofilament Ca2+ sensitivity through MLCK-induced phosphorylation of MLC2 is a novel mechanism contributing to the SFR in both atrium and ventricle.     

Differential regulation of SR calcium transporters by thyroid hormone in rat atria and ventricles

Thyroid hormone exerts positive inotropic effects on the heart mediated in part by its regulation of calcium transporter proteins, including sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2), phospholamban (PLB), and Na(+)/Ca(2+) exchanger (NCX). To further understand the potential cardiac chamber-specific effects of thyroid hormone action, we compared the triiodo-L-thyronine (T(3)) responsiveness of calcium transporter proteins in atrial versus ventricular tissues. Rats were rendered hypothyroid by ingestion of propylthiouracil, and a subgroup of animals was treated with T(3) for 7 days (7 microg/day by constant infusion). Atrial and left ventricular (LV) tissue homogenates were analyzed for expression of SERCA2, PLB, and NCX proteins by Western blot analysis. SERCA2 protein significantly decreased by 50% in hypothyroid LV and was normalized by T(3) treatment. In contrast, SERCA2 protein in atria was unaltered in the hypothyroid state. PLB protein expression significantly increased by 1.6- and 5-fold in the hypothyroid LV and atria, respectively, and returned to euthyroid levels with T(3) treatment. Expression of NCX protein showed a greater response to T(3) treatment in atria tissue than in ventricular tissue. Sarcoplasmic reticulum calcium cycling is determined in part by the ratio of SERCA2 to PLB. This ratio was sixfold higher in the atria compared with LV, suggesting that PLB may play a minor role in the regulation of SERCA2 function in normal atria. We conclude that calcium transporter proteins are responsive to thyroid hormone in a chamber-specific manner, with atria showing a greater change in protein content in response to T(3). The differential effect on atria may account for the occurrence of atrial rather than ventricular arrhythmias in response to even mild degrees of thyrotoxicosis.     

An Immunohistochemical Analysis of Tissue Thrombin Expression in the Human Atria

Objective

Thrombin, the final coagulation product of the coagulation cascade, has been demonstrated to have many physiological effects, including pro-fibrotic actions via protease-activated receptor (PAR)-1. Recent investigations have demonstrated that activation of the cardiac local coagulation system was associated with atrial fibrillation. However, the distribution of thrombin in the heart, especially difference between the atria and the ventricle, remains to be clarified. We herein investigated the expression of thrombin and other related proteins, as well as tissue fibrosis, in the human left atria and left ventricle.

Methods

We examined the expression of thrombin and other related molecules in the autopsied hearts of patients with and without atrial fibrillation. An immunohistochemical analysis was performed in the left atria and the left ventricle.

Results

The thrombin was immunohistologically detected in both the left atria and the left ventricles. Other than in the myocardium, the expression of thrombin was observed in the endocardium and the subendocardium of the left atrium. Thrombin was more highly expressed in the left atrium compared to the left ventricle, which was concomitant with more tissue fibrosis and inflammation, as detected by CD68 expression, in the left atrium. We also confirmed the expression of prothrombin in the left atrium. The expression of PAR-1 was observed in the endocardium, subendocardium and myocardium in the left atrium. In patients with atrial fibrillation, strong thrombin expression was observed in the left atrium.

Conclusions

The strong expression levels of thrombin, prothrombin and PAR-1 were demonstrated in the atrial tissues of human autopsied hearts.     

Comparison of time- and voltage-dependent K+ currents in myocytes from left and right atria of adult mice

Consistent differences in K+ currents in left and right atria of adult mouse hearts have been identified by the application of current- and voltage-clamp protocols to isolated single myocytes. Left atrial myocytes had a significantly (P < 0.05) larger peak outward K+ current density than myocytes from the right atrium. Detailed analysis revealed that this difference was due to the rapidly activating sustained K+ current, which is inhibited by 100 muM 4-aminopyridine (4-AP); this current was almost three times larger in the left atrium than in the right atrium. Accordingly, 100 muM 4-AP caused a significantly (P < 0.05) larger increase in action potential duration in left than in right atrial myocytes. Inward rectifier K+ current density was also significantly (P < 0.05) larger in left atrial myocytes. There was no difference in the voltage-dependent L-type Ca2+ current between left and right atria. As expected from this voltage-clamp data, the duration of action potentials recorded from single myocytes was significantly (P < 0.05) shorter in myocytes from left atria, and left atrial tissue was found to have a significantly (P < 0.05) shorter effective refractory period than right atrial tissue. These results reveal similarities between mice and other mammalian species where the left atrium repolarizes more quickly than the right, and provide new insight into cellular electrophysiological mechanisms responsible for this difference. These findings, and previous results, suggest that the atria of adult mice may be a suitable model for detailed studies of atrial electrophysiology and pharmacology under control conditions and in the context of induced atrial rhythm disturbances.     

Effect of 6-hydroxydopamine on the gene expression of Na+/Ca2+ exchanger in the rat heart

The Na+/Ca2+ exchanger (NCX) is an important component of the process of excitation-contraction coupling in the heart muscle. The level of gene expression as well as transport activities of this membrane structure is changed under pathological conditions like ischemic injury, myocardial infarction or diabetes. In this work we focused on the question whether the adrenergic modulation affects gene expression of the NCX in rat hearts. NCX mRNA levels were studied in the left cardiac atrium (divided into ganglionic and nonganglionic part) and also in the left ventricle of rats treated with 6-hydroxydopamine (6-OHDA) in control and stressed conditions. We have shown that administration of 6-OHDA decreases mRNA levels of NCX in both ganglionic and nonganglionic part of the left atrium and also in the left ventricle. This effect was not altered under combined administration of 6-OHDA and single immobilization stress. These data suggest that an activation of the adrenergic system can potentiate gene expression of the cardiac NCX.     

Parasympathetic control of the heart. I. An interventriculo-septal ganglion is the major source of the vagal intracardiac innervation of the ventricles.

The locations, projections, and functions of the intracardiac ganglia are incompletely understood. Immunocytochemical labeling with the general neuronal marker protein gene product 9.5 (PGP 9.5) was used to determine the distribution of intracardiac neurons throughout the cat atria and ventricles. Fluorescence microscopy was used to determine the number of neurons within these ganglia. There are eight regions of the cat heart that contain intracardiac ganglia. The numbers of neurons found within these intracardiac ganglia vary dramatically. The total number of neurons found in the heart (6,274 +/- 1,061) is almost evenly divided between the atria and the ventricles. The largest ganglion is found in the interventricular septum (IVS). Retrogradely labeled fluorescent tracer studies indicated that the vagal intracardiac innervation of the anterior surface of the right ventricle originates predominantly in the IVS ganglion. A cranioventricular (CV) ganglion was retrogradely labeled from the anterior surface of the left ventricle but not from the anterior surface of the right ventricle. These new neuroanatomic data support the prior physiological hypothesis that the CV ganglion in the cat exerts a negative inotropic effect on the left ventricle. A total of three separate intracardiac ganglia innervate the left ventricle, i.e., the CV, IVS, and a second left ventricular (LV2) ganglion. However, the IVS ganglion provides the major source of innervation to both the left and right ventricles. This dual innervation pattern may help to coordinate or segregate vagal effects on left and right ventricular performance.     

Effects of pituitary adenylate cyclase-activating polypeptide on canine atrial electrophysiology

We hypothesized that pituitary adenylate cyclase-activating polypeptide (PACAP) activates intracardiac postganglionic parasympathetic nerves and has a different effect than cervical vagal stimulation. We measured effective refractory period (ERP) and conduction velocity at four atrial sites [high right atrium (HRA), low right atrium (LRA), high left atrium (HLA), and low left atrium (LLA)] and minimum atrial fibrillation (AF) cycle length at 12 atrial sites during cervical vagal stimulation and after PACAP in 26 autonomically decentralized, open-chest, anesthetized dogs. PACAP shortened ERP to a similar extent at all four sites (HRA, 58 +/- 2.0 ms; LRA, 60 +/- 6.3 ms; HLA, 68 +/- 11.5 ms; and LLA, 60 +/- 8.3 ms). Low- and high-intensity vagal stimulation shortened ERP at the HRA, but not in the other atrial sites (low-intensity stimulation: HRA, 64 +/- 4.0 ms; LRA, 126 +/- 5.1 ms; HLA, 110 +/- 9.5 ms; and LLA, 102 +/- 11.5 ms; high-intensity stimulation: HRA, 58 +/- 4.2 ms; and HLA, 101 +/- 4.0 ms). Conduction velocity was not altered by any intervention. Minimum AF cycle length after PACAP was similar in both atria but was shorter in the right atrium than in the left atrium during vagal stimulation. After atropine administration, no interventions changed ERP. These results suggest that PACAP shortens atrial refractoriness uniformly in both atria through activation of intrinsic cardiac nerves, not all of which are activated by cervical vagal stimulation.     

K物质在大鼠心脏内的分布及其对心血管活动的作用

本工作应用特异性K物质放射免疫分析法测定了大鼠心脏的K物质样免疫活性,心房和心室含量分别为19.9±3.5和4.1±0.8pmol/g组织。心脏内的K物质样免疫活性物质主要以单一分子形式存在。用免疫组织化学方法证明K物质免疫活性存在于心脏神经纤维内。大鼠心肌杂交细胞株(CP8401)细胞上含有K物质特异性结合部位,KD为1.61×10~(-10)mol/L,Bmax为8.08×10~(-12)mol/L。用心肌杂交细胞和离体心脏进行体外实验,证明K物质可释放ANF,这种释放可为速激肽受体拮抗剂[D-Pro~2,D-Trp~(7,9)]-SP部份抑制。给麻醉大鼠静脉注射K物质可引起血压降低、心率加快、左心室内压和收缩速度下降。这一作用亦可被[D-Pro~2,D-Trp~(7,9)]-SP所部份抑制。应用大鼠离体灌流心脏模型,发现K物质可升高心脏灌流压、左心室收缩期峰压、左心室内压最大上升速率和加快心率、具有正性变时和变力性作用。 本工作提示,K物质存在于心脏神经纤维内,在心肌细胞上具有K物质的特异性结合位点。K物质可促进心肌细胞释放心钠素,并可调节心脏的功能。     

Comparison of atrial premature depolarization topography during vagal stimulation and humoral acetylcholine administration

Epicardial atrial mapping in open-chest dogs during different cholinergic influences has shown that, in acetylcholine administration and vagal stimulation, spatial distribution of atrial premature depolarisation (APDs) seems to be similar to prevalence of ectopic sources from both atria and atrial septum. Spatial distribution of the APDs in acetylcholine administration in the sinus node artery was limited to the region of this artery so that the APDs mainly arise from intercaval area of the right atrium and from atrial septum, but never from the left atrium. The latent pacemakers spread over both atria and atrial septum, could participate in initiation of cholinergically-induced APDs and atrial fibrillation. A direct effect of acetylcholine seems to be necessary for development of arrhythmic activity of the latent pacemakers.     

Rat corin gene: molecular cloning and reduced expression in experimental heart failure

Stored cardiac pro-atrial natriuretic peptide (pro-ANP) is converted to ANP and released upon stretch from the atria into the circulation. Corin is a serin protease with pro-ANP-converting properties and may be the rate-limiting enzyme in ANP release. This study was aimed to clone and sequence corin in the rat and to analyze corin mRNA expression in heart failure when ANP release upon stretch is blunted. Full-length cDNA of rat corin was obtained from atrial RNA by RT-PCR and sequenced. Tissue distribution as well as regulation of corin mRNA expression in the atria were determined by RT-PCR and RNase protection assay. Heart failure was induced by an infrarenal aortocaval shunt. Stretch was applied to the left atrium in a working heart modus, and ANP was measured in the perfusates. The sequence of rat corin cDNA was found to be 93.6% homologous to mouse corin cDNA. Corin mRNA was expressed almost exclusively in the heart with highest concentrations in both atria. The aortocaval shunt led to cardiac hypertrophy and heart failure. Stretch-induced ANP release was blunted in shunt animals (control 1,195 +/- 197 fmol.min(-1).g(-1); shunt: 639 +/- 99 fmol.min(-1).g(-1), P < 0.05). Corin mRNA expression was decreased in both atria in shunt animals [right atrium: control 0.638 +/- 0.004 arbitrary units (AU), shunt 0.566 +/- 0.014 AU, P < 0.001; left atrium: control 0.564 +/- 0.009 AU, shunt 0.464 +/- 0.009 AU, P < 0.001]. Downregulation of atrial corin mRNA expression may be a novel mechanism for the blunted ANP release in heart failure.     

Regional changes in ornithine decarboxylase activity and polyamine levels during thyroxine-induced cardiac hypertrophy

Ornithine decarboxylase activities (ODC) and polyamine levels were determined in five cardiac regions of the rat heart, following daily administration of 1 mg/kg of thyroxine, in the right and left atria, the right and left ventricles and the septum. The thyroxine stimulated ODC activity in all five regions of the heart. Enzyme activity in the left atrium and the septum peaked a day earlier than in other regions and the decline of ODC activity was slower. Putrescine in control animals was present in all regions except the right atrium, where its content was below detectable levels. Following the administration of thyroxine, the putrescine content of the left atrium, the right ventricle and the septum declined, while spermidine and spermine levels remained unchanged. In direct contrast to the other regions of the heart, thyroxine stimulated an increase in polyamines, as well as in weight which occurred exclusively in the left ventricle. These findings suggest a causal relationship between increased polyamines and hypertrophy.     

Hypoxia-induced downregulation of beta-adrenergic receptors in rat heart.

To test the desensitization hypothesis of cardiac beta-adrenergic receptors (beta-AR) in chronic hypoxia, the effect of 1, 3, 7, 15, and 21 days of exposure to hypobaric hypoxia (380 Torr) was evaluated in Wistar rats. Exposure to hypoxia for 1-15 days did not induce any change in right and left ventricular beta-AR density (Bmax) determined with [125I]iodocyanopindolol or in antagonist affinity. After 21 days, Bmax decreased by 24% in the left ventricle. In contrast, no change in beta-AR was shown in the right hypertrophied ventricle. Agonist affinity in the left ventricle was not altered, as shown by the analysis of displacement curves of isoproterenol (normoxia 185 +/- 26 nM, hypoxia 170 +/- 11 nM). Moreover, there was no significant decrease in adenylate cyclase activity (pmol.mg-1.min-1) in the left ventricle. In the right ventricle, a 21-day exposure to hypoxia led to a decrease in basal and maximal activity when stimulated by isoproterenol. A decrease in tissue norepinephrine content was observed after 7 days of hypoxia. In conclusion, these data support the beta-AR downregulation hypothesis as one of the mechanisms of myocardial adaptation to high altitude occurring after 2-3 wk of exposure to hypoxia. The regulation pathways of beta-AR may differ between left nonhypertrophied and right hypertrophied ventricles. No evidence of profound abnormality of signal transduction was shown.     

Plasma and atrial levels of atrial natriuretic peptide (ANP) in pulmonary hypertensive rats

Immunoreactive atrial natriuretic peptide (IR-ANP) was measured in plasma and atrium of normal and monocrotaline induced pulmonary hypertensive rats (PH rats). In these animals, there was right ventricular hypertrophy and right ventricular systolic pressure was elevated. Fourteen days after a single dose of monocrotaline (40 mg/kg), plasma IR-ANP concentrations were significantly elevated (964.3 +/- 63.0 pg/ml vs. 521.0 +/- 81.9 pg/ml in controls, p less than 0.001). Tissue levels of IR-ANP in the right atrium in PH rats was significantly lower than those in the controls (45.1 +/- 3.9 ng/mg vs. 240.5 +/- 10.4 ng/mg, p less than 0.001), while there was no significant difference in tissue levels of atrial IR-ANP in the left atrium between the two groups. Thus, development of pulmonary hypertension led to an increase in release of ANP from the right atrium.     

Localization and characterization of atrial natriuretic factor (ANF)-like peptide in the frog atrium

The distribution of ANF was studied in the heart of the frog (Rana ridibunda) using indirect immunofluorescence. ANF-like immunoreactivity was localized mainly in the right and left atrium, most of cardiocytes being intensively labelled. At the electron microscopic level, all secretory granules present in atrial cardiocytes contained ANF immunoreactive material. Using a specific radioimmunoassay, we found higher concentrations of ANF in the left atrium (208 +/- 25 ng/mg protein) than in the right atrium (120 +/- 16 ng/mg protein) whilst in the rat, the right atrium contains the highest ANF concentration. The concentration of ANF in the ventricle was 10 times lower than in the whole atrium (32 +/- 4 ng/mg protein). Sephadex G-50 gel filtration of atrial extracts showed that ANF-like immunoreactivity eluted in three peaks. Most of the immunoreactivity corresponded to high molecular weight material eluting at the void volume while 20% of the material co-eluted with synthetic (Arg 101-Tyr 126) ANF. These results indicate that frog cardiocytes synthetize a peptide which is immunologically and biochemically related to mammalian ANF.     

Subcellular Ca2+ transport in different areas of dog heart

Calcium transport and ATPase activities were determined in the heavy and mitochondrial fractions isolated from the left and right atria as well as ventricles of dogs. Ultrastructural distribution of these organelles in different areas of the myocardium was also examined. Calcium binding, calcium uptake, and calcium ATPase activities of the atrial microsomes were lower than those of the ventricles. On the other hand, mitochondrial calcium binding and uptake activities in the right atrium were higher than those in other areas. The mitochondrial total ATPase activities in the atria were also higher than those in the ventricles. Mitochondrial as well as microsomal yields from ventricles were significantly higher. Size and number of mitochondria in the ventricles were greater whereas no striking difference in the distribution of sarcoplasmic reticulum was apparent in different areas of the heart. Poorly developed calcium transport functions in the atrial microsomes may be one of the factors responsible for the generation of lower contractile force in this tissue in comparison with the ventricle.