The effects of manganese ions on the contraction of the frog's heart

1. The effects of Mn(2+) in particular but also of Ni(2+), Co(2+), Cd(2+), verapamil and D600 on the contraction of isolated frog atrial trabeculae have been investigated. Contraction was initiated either by electrical stimulation, or by raising the [K](o) or by lowering the [Na](o).2. Mn ions like Ca ions cause a hyperpolarization of the cell membrane and a rise in the threshold for the action potential and twitch. Mn ions, particularly at low concentrations, reduce the overshoot of the ventricular action potential.3. Mn ions reduce the strength of the regularly evoked heart beats. Prolonged exposure, in beating hearts, results in a rise in resting tension and often a small recovery of the heart beat.4. In normal Ringer solution and in Ringer free of Na ions, the addition of Mn causes the tension-depolarization curve to be displaced by an amount equivalent to an 18 mV hyperpolarization of the membrane potential for a tenfold increase in the divalent cation concentration.5. Mn, Co, Ni and Cd ions all cause a marked reduction in the tension generated by exclusion of Na ions from the bathing fluid. In the presence of these divalent cations the contracture divides into an initial phasic and a later tonic contraction. This inhibition is reversed by raising the [Ca](o), while the tension developed during the initial phasic contraction varies with the [Ca](o)/[Mn](o) quotient.6. A similar tonic contracture is initiated after exposure to Na-free fluid containing a high [Mn](o) by the addition of a small concentration of Na, Li, hydrazinium or hydroxylammonium ions.7. The organic ;Ca antagonists' verapamil and D600 have little effect on the contracture induced by lowering [Na](o) even after prolonged exposure at relatively high concentrations but they do inhibit the twitch contraction and the K contractures.8. The effects of Mn on the Na-withdrawal contracture of frog heart can be interpreted in terms of an exclusively extracellular effect where Mn ions resemble Na ions in their action, and both antagonize the movement of Ca across the cell membrane.9. The experimental evidence suggests that the K contracture in frog heart is initiated by a mechanism which is, in some ways different to that underlying the Na-withdrawal contracture, and may involve two different sources of activator Ca.10. The several different effects of Mn on the frog heart probably reflects the ability of this cation to interfere with many processes involving Ca, and that there are a number of such processes involved in the results described in this work. The effects of Mn are more complex than might be generally supposed.     

人胚心静脉窦和传导系统的早期发育

目的 探讨早期人胚心静脉窦及传导系的发生发育机制. 方法 用抗α-平滑肌肌动蛋白(α-SMA)、抗α-横纹肌肌动蛋白(α-SCA)和抗结蛋白(DES)抗体对29例C10～C16期人胚心连续切片行免疫组织化学染色. 结果 人胚发育C12～C13期,系统静脉汇集形成的静脉窦出现于心包腔尾端原始横膈间充质中,静脉窦壁间充质细胞逐渐分化为α-SCA阳性的静脉窦心肌细胞.C14期,心包腔的扩张使静脉窦进入心包腔内,参与了右心房的形成.DES阳性传导系心肌的分化始于C10期心房室管右侧壁,随发育逐渐向室间沟心肌扩展,发育为房室传导系的希氏束、左右束支及心室腔面的小梁心肌.在心房,DES表达首先出现于C11期心房背侧壁,在C13期,可见静脉窦左背侧壁α-SCA、α-SMA、DES阳性心肌带与左心房底部、房室管背侧壁相延续,这条心肌带可能参与了人胚心静脉窦至房室管传导系的发育.C14～C16期,DES强阳性染色从窦房结经左、右静脉瓣及心房的背、腹侧壁延伸至房室管右侧壁,可能是原始的心房传导通路. 结论 心包腔尾端原始横膈间充质是人胚静脉窦心肌发生区,原始横膈间充质细胞逐渐分化为心肌细胞,添加到人胚心管静脉端,形成心静脉窦心肌.人胚心传导系心肌的分化始于房室管,随心管发育逐渐向动、静脉端扩展,在C16期,已分化为形态清晰可辨的DES阳性胚胎心传导系.     

The nature of the superior sinus venosus defect

The location, and morphology, of the superior sinus venosus interatrial communication remains contentious. As part of a clinical study, we examined anatomic specimens and echocardiograms so as to clarify the arrangement of the normal atrial septal structures, and compared them with the arrangement found in the superior sinus venosus defect. The pathognomonic diagnostic criterion in the abnormal hearts was overriding of the intact muscular rim of the oval fossa by the mouth of the superior caval vein. This muscular rim is, in reality, a tube of myocardium which encloses a core of extracardiac adipose tissue. Understanding of this anatomic conundrum clarifies the understanding of the structures of both the normal atrial septum and sinus venosus defects. Clin. Anat. 11:349–352, 1998. © 1998 Wiley-Liss, Inc.     

Calcium-sodium antagonism on the frog's heart: a voltage-clamp study.

1. In double sucrose-gap voltage-clamped frog atrial fibres the influence of [Ca]o and [Na]o on membrane current and contraction was investigated. 2. The slow (secondary) inward current varied with [Ca]o but was almost insensitive to changes in [Na]o. In contrast, the phasic (transient) contraction initiated by the slow inward current was affected by both [Ca]o and [Na]o. 3. With moderate changes of [Ca]o and [Na]o from normal, the strength of phasic contraction at a given depolarization followed the [Ca]o/[Na]2o ratio approximately. This was best seen at membrane potentials near zero level. 4. Under the same conditions, tonic (sustained) contractions associated with prolonged depolarizations were strictly correlated to the [Ca]o/[Na]2o ratio at any potential. No interrelation between tonic tension and steady-state current was found. 5. With extensive changes in [Ca]o and [Na]o, the sensitivity of both phasic and tonic tension to the [Ca]o/[Na]2o ratio declined, the negative effect of [Na]o becoming smaller than was expected from this ratio. 6. In Na-free choline-Ringer, a strong contracture developed followed by a spontaneous relaxation. Starting from the relaxed state, application of depolarizing clamps gave rise to phasic contractions with a very slow relaxation while tonic contractions were apparently lacking. 7. The results are interpreted in terms of an energy-dependent carrier mechanism exchanging one Ca for two Na ions across the cell membrane. The model implies a strong asymmetry in the rate constants governing the chemical reactions on both sides of the membrane. The system is thought to operate close to equilibrium at any potential, thereby determining the steady level of myoplasmic Ca. The equilibrium itself is considered to shift upon depolarization. Assuming that [Na]i is constant, the steady level of [Ca]i is expected to be proportional to the [Ca]o/[Na]2o ratio, the scale factor being a function of membrane potential. 8. The carrier model suggests the occurrence of a depolarization-induced inward transfer of Ca which might be involved in the generation of tonic contractions. 9. The apparent lack of tonic contractions in the absence of external Na ions may be explained by a suppression of carrier-mediated Ca influx normally occurring upon depolarization. 10. The antagonistic effects of [Ca]o and [Na]o on phasic contraction are understood as being due to alterations of the Ca pumping system rather than changes in slow inward current.     

Developmental aspects of the sinus valves and the sinus venosus septum of the right atrium in human embryos

Summary In 32 human embryos from 5 to 27 mm of length, stages 13 to 23 (according to the Carnegie system of stages), the contributions of the sinus venosus septum and the right sinus valve of the right atrium to the formation of the Eustachian and Thebesian valve were examined by scanning electron microscopy. The sinus septum takes part in the subdivision of the right sinus valve into the Eustachian and the Thebesian valves. From its first origin the sinus septum forms a septal structure between the orifices of the right hepatic vein (hepatic portion of the inferior caval vein), the precursor of the inferior caval vein, and the left horn of the sinus venosus, the precursor of the coronary sinus. Before the incorporation of the sinus venosus into the right atrium, it has an intra-sinusal position, and extends between the bases of the left and the right sinus valve. During the incorporation of the sinus venosus into the right atrium the sinus septum receives an intra-atrial position, and its positional relationships to the sinus valves and the orifices of the corresponding veins remain unchanged in principle. Due to the connection between the sinus septum and the right sinus valve, after completion of the incorporation of the sinus, the superior portion of the right sinus valve branches y-like into a lateral limb, (i.e. its original inferior portion) and into a medial limb, (i.e. the sinus septum). Thus, the Eustachian valve is formed by the superior portion of the right sinus valve and the sinus septum; whereas the Thebesian valve is formed by the inferior portion of the right sinus valve. The normal variations in the configuration of the Eustachian and the Thebesian valves are supposed to be caused by differential growth of the constituents of the different portions of the valves. This work was supported by the Stiftung Volkswagenwerk (I/63 363). Gratefully dedicated to Professor Erich Blechschmidt on the occasion of his 85th birthday     

The mechanism of insulin's toxic effect on a frog's heart

Summary The author suggests that the negative effect of toxic doses of insulin on cardiac activity is possibly caused by depression of the activity of the tissue sulfhydryl groups. To obtain experimental verification of this suggestion, the author studied the action of urea on the work of the isolated frog's heart under conditions of insulin intoxication. Following the arrest of the cardiac activity caused by toxic doses of insulin, urea administration helped restore the contractile myocardial function and the ECG indices. Such an effect is evidently due to the fact that urea, which has the ability to loosen the protein molecule and liberate the tissue sulfhydryl groups, brings about the restoration of disturbed processes in the cardiac muscle.(Presented by V. N. Chernigovskii, Active Member of the AMN SSSR) Translated from Byulleten Èksperimental'noi Biologii i Meditsiny Vol. 49, No. 4, pp. 75–78, April, 1960     

The dual effect of calcium on the action potential of the frog's heart

1. Using ventricle strips of the frog's heart stimulated at the low rate of about 1 shock/min intracellular action potentials were recorded under conditions of varying calcium concentrations.2. Overshoots of action potentials were increased by about 18.3 mV as a result of a 10-fold increase, within the range of 0.1-5 mM, of the calcium concentration.3. A similar effect was obtained by strontium, but magnesium was ineffective.4. The increase of the overshoot by high calcium was associated with an increased rate of rise of the potential during the later part of its ascending phase. The initial fast upstroke remained unaltered.5. Another effect, a depression of the overshoot, developed during periods of repetitive stimulation, at the rate of 20/min, and this was followed by a gradual recovery during subsequent periods of rest.6. The depression of the overshoot increased with increasing calcium concentrations reaching values of over 40 mV.7. High concentrations of strontium and low concentrations of sodium also induced depression of the overshoot, but high magnesium was ineffective.8. A tentative hypothesis has been proposed attributing these two effects: (a) to an entry of calcium through the excitable membrane thus contributing to the ionic inward current, and (b) to a resulting accumulation of calcium in some cellular store.     

Direct contact between a neuron soma and myocardial cells; an electronmicroscopic finding in the sinus venosus of the turtle heart

Electron microscopy of the turtle sinus venosus shows an unusual neuron soma which is immediately surrounded by myocardial cells so as to form a somato-muscular complex. Studies of 36 sections cut through this neuron soma indicate that 27.4% of the somal surface studied is directly covered by cardiac muscle cells without any intervening basal lamina. Similarly, 18.8% of the somal surface studied is in contact with unmyelinated axons which at places make typical axosomatic synapses. A coupling of peripheral cisterns of the sarcoplasmic reticulum and the sarcolemma exists at the somato-muscular contiguity as well as at the border between cardiac muscle cells. It is suggested that neural influences upon the pacemaking activity of the turtle heart sinus can well be exerted through the somato-muscular pathway. Additionally, an axon which is presynaptic to the neuron soma has been observed to be simultaneously in a synaptic relation with a cardiac muscle cell; a remarkable deviation from the classical picture of the efferent nervous outflow to the heart.     

Membrane currents underlying activity in frog sinus venosus.

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential.2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2.0 x 10(-6) g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing.3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca(2+)/Na(+)) current, I(si), of other cardiac tissues. The threshold for I(si) is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization.4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions.5. Outward current decay is not a simple exponential, and Hodgkin-Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the ;plateau' range of the sinus action potential.6. These results are compared with other recently published voltage clamp data from the rabbit sino-atrial node.7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, I(si).