Impulse propagation from the SA-node to the ventricles

Summary Normally the pacemaker of the mammalian heart is located in the sinus node. In the rabbit the sinus node can be subdivided into two regions, the center of the node where the impulse originates and the border zone through which the impulse is conducted towards the atrium. Conduction properties of both regions were investigated. It appeared that conduction velocity increases and refractoriness decreases when one goes from the nodal center towards the atrium. The tissue mass of the atrium is large in comparison to the sinus node and normally the resting membrane potential of atrial fibers is more negative than that of nodal fibers; consequently, a potential difference exists causing a current flow between both areas. Evidently this hyperpolarizing current flow depresses impulse formation in the border zone fibers which have better intrinsic pacemaker properties than fibers in the nodal center. If the impulse has reached the atrium it is conducted with a relatively high safety factor and will reach the AV node in principle without difficulty. The AV node, if deprived of sinus nodal dominance, develops spontaneous activity originating from the lower nodal fibers. Also in this structure, electrotonic depression by surrounding tissue causes deceleration of the pacemaker.     

Evidence of a subsidiary atrial pacemaker in the crista terminalis of the rabbit heart

Summary The crista terminalis (CT) with musculi pectinati was isolated from the right atrium: it discharged at a frequency intermediate to that of the 2 nodes. Pacemaker action potentials were recorded from the CT deep layer fibers. The results suggest the presence of a subsidiary atrial pacemaker in the CT deep layer.     

Membrane currents in cardiac pacemaker tissue

The present work is a brief survey of the mechanism of the cardiac pacemaker in sinoatrial node cells. Information on the pacemaker mechanism in cardiac tissue has been greatly enhanced by the development of the single cell isolation technique and the patch clamp technique. These methods circumvent to a large extent the difficulties involved in voltage clamping multicellular preparations. The calcium current (ICa), delayed rectifier potassium current (IK), transient outward current (Ito;IA), and the hyperpolarization activated inward current (Ih or If) were found both in whole cell preparations and in single channel analysis. The physiological significance of these currents, together with the exchange current systems for the pacemaker depolarization are discussed.     

The effects of manganese and barium on the cardiac pacemaker current, if, in rabbit sino-atrial node myocytes

The isolation of ionic fluxes contributing to electric currents through cell membranes often requires block of other undesired components which can be achieved, among others, by divalent cations. Mn2+ and Ba2+ are often used, for example, to block Ca and K currents. Here we have investigated the effects of these two cations on the properties of the hyperpolarization-activated pacemaker current if, in rabbit sino-atrial node myocytes, as obtained by voltage clamp analysis. We find that 2 mM Mn2+ shifts the if activation curve by 3.2 +/- 0.3 mV towards more positive values. However, when 1 mM Ba2+ is also added, the positive shift is more than halved (1.3 +/- 0.2 mV). We find, too, that in the absence of blocking cations the ACh-induced if inhibition is slightly higher than in their presence. These results indicate that the alteration of if kinetic properties by Ba2+ plus Mn(2+)-containing solutions is minimal.     

Conduction of the impulse in the ischemic myocardium--implications for malignant ventricular arrhythmias

Ventricular arrhythmias occurring consequent to regional disturbances of myocardial perfusion are the most frequent cause of sudden cardiac death. They are related to marked changes of impulse propagation in the ischemic region, which consist of circulating excitation with re-entry. Mapping of the impulse during ventricular tachycardias and ventricular fibrillation shows that the circus movements change their shape and localization from beat to beat. Zones of tissue which block the impulse during one beat may conduct the impulse at a fast rate during the next beat. The main cause underlying this behavior is the depression of the ischemic action potential. This depression is caused by the partial inactivation and the prolonged recovery of the rapid sodium inward current. In addition to the decrease in resting potential, other factors, such as acidosis, contribute to the inactivation of the inward currents generating the upstroke of the action potential. An increase of coupling resistance between myocardial cells and/or an increase of extracellular resistance appear to be less important for explaining conduction disturbances in acute ischemia.     

Conduction of the impulse in the ischemic myocardium — implications for malignant ventricular arrhythmias

Summary Ventricular arrhythmias occurring consequent to regional disturbances of myocardial perfusion are the most frequent cause of sudden cardiac death. They are related to marked changes of impulse propagation in the ischemic region, which consist of circulating excitation with re-entry. Mapping of the impulse during ventricular tachycardias and ventricular fibrillation shows that the circus movements change their shape and localization from beat to beat. Zones of tissue which block the impulse during one beat may conduct the impulse at a fast rate during the next beat. The main cause underlying this behavior is the depression of the ischemic action potential. This depression is caused by the partial inactivation and the prolonged recovery of the rapid sodium inward current. In addition to the decrease in resting potential, other factors, such as acidosis, contribute to the inactivation of the inward currents generating the upstroke of the action potential. An increase of coupling resistance between myocardial cells and/or an increase of extracellular resistance appear to be less important for explaining conduction disturbances in acute ischemia.     

Frequency gradient in the autorhythmicity of the pyeloureteral pacemaker system

The pacemaker properties of the various regions of isolated segments of the rabbit renal pelvis were examined. The results show that pacemaker frequency and waveform of contraction change significantly within the renal pelvis. The highest frequency was encountered at the fornix, while the ureteropelvic junction is lowest.     

Frequency gradient in the autorhythmicity of the pyeloureteral pacemaker system

Summary The pacemaker properties of the various regions of isolated segments of the rabbit renal pelvis were examined. The results show that pacemaker frequency and waveform of contraction change significantly within the renal pelvis. The highest frequency was encountered at the fornix, while the ureteropelvic junction is lowest.This work was supported by NIH Grant No AM19366.     

The effects of manganese and barium on the cardiac pacemaker current,i f,in rabbit sino-atrial node myocytes

Summary The isolation of ionic fluxes contributing to electric currents through cell membranes often requires block of other undesired components which can be achieved, among others, by divalent cations. Mn²⁺ and Ba²⁺ are often used, for example, to block Ca and K currents. Here we have investigated the effects of these two cations on the properties of the hyperpolarization-activated pacemaker current i_f, in rabbit sino-atrial node myocytes, as obtained by voltage clamp analysis. We find that 2 mM Mn²⁺ shifts the i_f activation curve by 3.2±0.3 mV towards more positive values. However, when 1 mM Ba²⁺ is also added, the positive shift is more than halved (1.3±0.2 mV). We find, too, that in the absence of blocking cations the ACh-induced i_f inhibition is slightly higher than in their presence. These results indicate that the alteration of i_f kinetic properties by Ba²⁺ plus Mn²⁺-containing solutions is minimal.     

Effects of hyperpolarizing currents on the action potentials of nodal and perinodal sino-atrial cells of the rabbit heart]

A technique of focal polarization allowed us to confirm that the action potentials of the true rabbit heart pacemaker cells possess a rapid sodium channel normally inactivated because of the low value of the take-off potential of this tissue. The latent pacemaker cells are regular sinocaval cells depolarized as a consequence of the proximity of true pacemaker cells.     

Simple technic for culture of locus coeruleus nucleus in the newborn mouse]

The dissecting procedure and tissue culture technique on collagen coated coverslips in Leighton tubes, of newborn Mouse nucleus locus coeruleus and the regular histofluorescence demonstration of catecholaminergic fibers in the outgrowth zone are described. This simple method allows 10 day--long experiments .     

Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA

Voltage-dependent K+ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K+ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K+ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K+ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K+ channels in frog nerves depends on fiber diameter. The size dependence was used to determine the relative sensitivity of nodal and internodal K+ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K+ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K+ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.     

Splenic architecture reflected in the connective tissue structure of the human spleen

An analysis of the connective-tissue structure of the human spleen can give us information about the basic architecture of the organ. The most important part of the spleen is the lienic center around which the subcapsular zone forms an envelope, like a mantle. This zone has but little depth and develops superficially. The tangential radial beam net ('Tangentialbalkennetz') is formed partly by the radial trabeculae of the capsule and partly by the outer branches of the arbor trabecularis. This arbor divides into 5-6 branching orders. The branches of orders 1 to 3 surround the parenchyma of the spleen center's inner layer. The lienic lobuli which are found between the branches are relatively large and are connected very extensively with their parenchyma. The branches of orders 4, 5, and 6 enclose the lienic lobuli of the outer layer of the spleen center. The splenic lobuli are defined by the vascular course. Mostly they are provided with one or two arterial influxes and, as a rule, with only one venous drain. Their mutual delimitation is more of a functional than of a morphological nature. This led von Herrath to coin the term 'functional spleen lobuli'. The lienic envelope lies between the inside of the capsule and the outermost branchings of the arbor trabecularis. This arbor is subdivided, by the radial trabeculae, which never have any vessels, into elongated lobuli and serves first and foremost to regulate pressure. The lattice fibers are of high tensile strength and are extensions of the collagenous fibers seen at the microscopic level.     

HCN channels contribute to the intrinsic activity of cochlear pyramidal cells

A hyperpolarization-activated current recorded from the pyramidal cells of the dorsal cochlear nucleus was investigated in the present study by using 150- to 200-m-thick brain slices prepared from 6- to 14-day-old Wistar rats. The pyramidal neurones exhibited a slowly activating inward current on hyperpolarization. The reversal potential of this component was –32 ± 3 mV (mean ± SE, n = 6), while its half-activation voltage was –99 ± 1 mV with a slope factor of 10.9 ± 0.4 mV (n = 27). This current was highly sensitive to the extracellular application of both 1 mM Cs⁺ and 10 M ZD7288. The electrophysiological properties and the pharmacological sensitivity of this current indicated that it corresponded to a hyperpolarization-activated non-specific cationic current (I_h). Our experiments showed that there was a correlation between the availability of the h-current and the spontaneous activity of the pyramidal cells, suggesting that this conductance acts as a pacemaker current in these neurones. Immunocytochemical experiments were also conducted on freshly isolated pyramidal cells to demonstrate the possible subunit composition of the channels responsible for the genesis of the pyramidal h-current. These investigations indicated the presence of HCN1, HCN2 and HCN4 subunits in the pyramidal cells.Received 15 May 2003; received after revision 26 June 2003; accepted 21 July 2003     

Calcium channel modulation by beta-adrenergic neurotransmitters in the heart

Calcium ions play a crucial role in the regulation of the heart beat. During each action potential Ca2+ ions flow into the cell and are directly and indirectly involved in generation of pacemaker potentials and of contractile force. Adrenergic and cholinergic neurotransmitters modulate Ca2+ influx. The most detailed analysis has been made on the mechanism of the beta-adrenergic effect on calcium channels in cardiac cell membranes. This is briefly summarized in a personal account, while for more detailed information the reader is referred to more extensive recent reviews.     

Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA

Summary Voltage-dependent K⁺ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K⁺ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K⁺ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K⁺ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K⁺ channels in frog nerves depends on fiber diameter. This size dependence was used to determine the relative sensitivity of nodal and internodal K⁺ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K⁺ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K⁺ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.     

Potassium transfer from brain to blood during sustained hyponatraemia in the newborn calf

Summary The effect of dilutional hyponatraemia on cerebral blood flow and oxygen consumption, and net transfer of K⁺ to the circulation from brain tissue drained by the sagittal sinus was investigated in anaesthetized calves. Cerebral blood flow decreased, and net transfer of K⁺ to the circulation increased during hyponatraemia.Acknowledgments. The expert assistance of Miss B.N. O'Connor, Miss D. McNaughton and Mr P.M.M. Bircham is gratefully acknowledged.     

Über eine spontane Extrasystolie im Schrittmachersystem des Tunicatenherzens (Ciona intestinalis L.)

Summary Some experimental results on action potential (EKG) in the pacemaker system of the tunicata heart (Ciona intestinalis) are presented. Synchronous records of both end and central heart regions show a spontaneous chance of the electrical activity in the middle of the heart tube, just before the periodic reversal of the direction of the pulsating wave starts. Extra systoles in the central pacemaker influence the terminal centres and provoke reversal.

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Herrn Prof.W. v. Buddenbrock zum 80. Geburtstag.