Atrioventricular Nodal Cells Research Articles

Morphological study of sarcoplasmic reticulum in the atrioventricular node and bundle cells in guinea pig hearts.

The osmium-ferrocyanide method for staining of the sarcoplasmic reticulum (SR) was used for a morphological investigation of the various components of the SR in the atrioventricular node and bundle (AVNB) cells of guinea pig hearts. On the basis of light microscopic observations, the AVNB tissue in guinea pig hearts can be divided into five regions: atrionodal junction, midnode, proximal bundle, distal bundle, and bundle branches. Electron microscopic observations revealed two types of junctional SR (j-SR) saccules in the cells from all the regions of AVNB tissue. One is similar to that seen in the working cardiac cells, i.e., flattened saccules with junctional granules. The second type is dilated and contains electron-dense granular material throughout its lumen. The flattened type is seen more often than the dilated type in atrionodal junctional cells and midnode cells, whereas the dilated type occurs more often in distal bundle cells and bundle branch cells. In most cells from the atrionodal junction and midnode regions, the j-SR saccules are apposed more often to sarcolemmal areas associated with nonspecialized regions of intercellular junctions than to other sarcolemmal areas. This distribution was not found in the distal bundle and bundle branch cells. Free SR tubules around the myofilament bundles are poorly developed in the midnode cells, generally in accord with the extent of development of myofibrils. Z-tubules are found in cells from all regions but are poorly developed in midnode cells. Corbular SR vesicles are found in cells from all the regions of AVNB tissues but are rare in midnode cells. Thus, each of the regions in the AVNB tissue has a different, characteristic distribution of SR components. Because of their possible relationship to the regulation of the intracellular concentrations of calcium, these differences in SR morphology may contribute to the diverse physiological properties of the different regions of the AV node and bundle.

Characterization of the effects of histamine on the transmembrane electrical activity of guinea-pig and rabbit SA- and AV-node cells.

The effects of histamine on the transmembrane electrical activity of cells of small preparations (0.5 X 0.5 mm) of guinea-pig and rabbit sinoatrial- and atrioventricular-nodes were studied. Histamine at concentrations above 10(-7) mol/l increased the firing rate, the rate of diastolic depolarization, the maximum diastolic potential, the amplitude and the maximum rate of depolarization of the action potential of pacemaker cells of rabbit and guinea-pig sinoatrial cells and rabbit atrioventricular cells. These effects were antagonized by the H2-receptor blocker cimetidine (2.5 X 10(-6)mol/l) but they were not modified by the H1-receptor blocker chlorphenamine (2.5 and 5 X 10(-6)mol/l). Small preparations of guinea-pig atrioventricular node did not exhibit spontaneous activity, but it was induced by histamine and blocked by cimetidine. Histamine increased the maximum upstroke velocity of propagated action potential of cells of the central part of complete atrioventricular node in both species studied. These effects were blocked by cimetidine, but not by chlorphenamine. It is concluded that the increase in automaticity induced by histamine in guinea-pig and rabbit sinoatrial and atrioventricular nodes was due to stimulation of H2-receptors. Histamine did not depress electrical activity of atrioventricular node cells, but rather increased it. This effect was due to H2-receptor stimulation.

Simulation analysis of excitation conduction in the heart: Propagation of excitation in different tissues

The normal excitation and conduction in the heart are maintained by the coordination between the dynamics of ionic conductance of each cell and the electrical coupling between cells. To examine functional roles of these two factors, we proposed a spatially-discrete model of conduction of excitation in which the individual cells were assumed isopotential. This approximation was reasoned by comparing the apparent space constant with the measured junctional resistance between myocardial cells. We used the four reconstruction models previously reported for five kinds of myocardial cells. Coupling coefficients between adjacent cells were determined quantitatively from the apparent space constants. We first investigated to what extent the pacemaker activity of the sinoatrial node depends on the number and the coupling coefficient of its cells, by using a one-dimensional model system composed of the sinoatrial node cells and the atrial cells. Extensive computer simulation revealed the following two conditions for the pacemaker activity of the sinoatrial node. The number of the sinoatrial node cells and their coupling coefficients must be large enough to provide the atrium with the sufficient electric current flow. The number of the sinoatrial node cells must be large so that the period of the compound system is close to the intrinsic period of the sinoatrial node cell. In this simulation the same sinoatrial node cells produced action potentials of different shapes depending on where they were located in the sinoatrial node. Therefore it seems premature to classify the myocardial cells only from their waveforms obtained by electrical recordings in the compound tissue. Second, we investigated the very slow conduction in the atrioventricular node compared to, for example, the ventricle. This was assumed to be due to the inherent property of the membrane dynamics of the atrioventricular node cell, or to the small value of the coupling coefficient (weak intercellular coupling), or to the electrical load imposed on the atrioventricular node by the Purkinje fibers, because the relatively small atrioventricular node must provide the Purkinje fibers with sufficient electric current flow. Relative contributions of these three factors to the slow conduction were evaluated using the model system composed of only the atrioventricular cells or that composed of the atrioventricular and Purkinje cells. We found that the weak coupling has the strongest effect. In the model system composed of the atrioventricular cells, the propagation failure was not observed even for very small values of the coupling coefficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Myosin types and fiber types in cardiac muscle. III. Nodal conduction tissue.

The sinoatrial (SA) and atrioventricular (AV) nodes are specialized centers of the heart conduction system and are composed of muscle cells with distinctive morphological and electrophysiological properties. We report here results of immunofluorescence and immunoperoxidase studies on the bovine heart showing that a large number of SA and AV nodal cells share a distinct type of myosin heavy chain (MHC) which is not found in other myocardial cells and can thus be used as a cell-type-specific marker. The antibody used in this study was raised against fetal skeletal myosin and reacted with fetal skeletal but not with adult skeletal MHCs. Both atrial and ventricular fibers, as well as fibers of the ventricular conduction tissue were unlabeled by this antibody. Specific reactivity was exclusively seen in most cells in the central portions of the SA and AV nodes and rare cells in perinodal areas. However, a number of nodal cells, particularly those located in the peripheral nodal regions, were unreactive with this antibody. The myosin composition of nodal tissues was also explored using two antibodies reacting specifically with alpha-MHC, the predominant atrial isoform, and beta-MHC, the predominant ventricular isoform. Most nodal cells were reactive for alpha-MHC and a number of them also for beta-MHC. Variation in reactivity with the two antibodies was also observed in perinodal areas: at these sites a population of large fibers reacted exclusively for beta-MHC. These findings point to the existence of muscle cell heterogeneity with respect to myosin composition both in nodal and perinodal tissues.

Cytofluorometric nuclear DNA determinations on the atrioventricular nodal cells in human hearts.

In the human heart, it is well known that the polyploidization of working heart-muscle cells increases in proportion to increases in heart weight, but there has been no investigation of the process of polyploidization in the specialized heart-muscle cells of the cardiac conduction system which have a nerve-like function. In order to investigate the process of polyploidization in these cells, the nuclear DNA content of atrioventricular nodal cells was measured using cytofluorometry. Tissue samples taken from autopsied hearts without arrhythmias were embedded in paraffin blocks after Carnoy fixation. Blocks containing the atrioventricular conduction system were cut according to the serial sectioning method of Lev et al. The compact atrioventricular nodes were removed from thick paraffin sections (150 micron) under a stereomicroscope. The cells were then isolated by enzyme digestion and ultrasonic treatment. Smears of the isolated cells were double stained with azocarmin-G and acriflavine-Feulgen. Cytofluorometric DNA determinations of the DNA content of atrioventricular nodal cells were performed. Atrioventricular nodes were found to be composed of a large number of diploid cells and a small number of tetraploid cells. No octaploid cells were found. These findings reveal that the process of polyploidization in atrioventricular nodal cells is different from that found in working heart-muscle cells.

The Effects of Indecainide, a New Antidysrhythmic Drug, on Nodal Tissues in the Isolated Rabbit Heart

The effects of indecainide, previously shown to be a class 1c antiarrhythmic drug restricting fast inward current, have been studied on rabbit sinoatrial (SA) node and atrioventricular (AV) node. Indecainide at concentrations up to 2.9 mumol/L in 5 preparations did not produce a sinus bradycardia, nor reduce the maximum rate of rise of the intracellular action potential of sinus node cells, but it did antagonize the tachycardia induced by increasing the extracellular calcium concentration. Indecainide slightly prolonged AV conduction time [from 49.07 +/- 4.43 ms to 57.37 +/- 0.90 ms at 2.9 mumol/L (means +/- SEM in four preparations)], but this small delay could be attributed to slowing of conduction in atrial fibres leading to the node, rather than to an effect on the AV nodal cells themselves. It is concluded that indecainide does not block channels carrying inward calcium current in nodal tissues.

Observations on the fine structure of nodal, Purkinje and working myocardial cells isolated from rabbit hearts.

Sinoatrial and atrioventricular nodal cells as well as Purkinje and working myocardial cells isolated enzymatically from rabbit hearts were examined by transmission electron microscopy. The cardiac cell fine structure remained well organized in the storage solution after isolation. In normal Tyrode solution, the nodal cells changed from spindle shaped to spherical, whereas the shapes of Purkinje and working myocardial cells remained unchanged. The nodal cell fine structure became disorganized with respect to its sarcomeric arrangement in normal Tyrode solution. This was assumed to result from a combination of several factors seen in the nodal cells: the loss of the normal anchoring of the myofibrils at the previous intercalated discs, breakdown of the Z bands and the alteration of the integrity of the intermediate filaments. Also, extensive restoration of plasma membrane damaged by of the intermediate filaments. Also, extensive restoration of plasma membrane damaged by the isolation procedure was observed in this solution. This might correspond to the retention of the normal physiological properties of the plasma membrane of the nodal cells despite gross morphological changes undergone in normal Tyrode solution.

Transient outward current carried by potassium and sodium in quiescent atrioventricular node cells of rabbits.

Single atrioventricular node cells were dispersed by treating the rabbit heart with collagenase. In Tyrode's solution, the cells became rounded, and about 20% of them showed spontaneous activity, whereas the rest remained quiescent. When those quiescent cells were whole-cell clamped, depolarizing clamp pulses from the holding potential of -83 mV induced an outward current which decayed quickly, with a time course similar to that of the transient outward current in the Purkinje fiber. The amplitude of the current became larger when progressively more positive clamp pulses were given from a very negative holding potential. The inactivation time course of this current consisted of two exponential components. Single-channel current recordings from those cells revealed a class of channels that activated more frequently during the initial part of depolarizing pulses. Summation of those unitary currents reproduced activation and inactivation time courses of the macroscopic current well, suggesting that this channel corresponds to the transient outward current. The current-voltage relationship of the channel was linear with the slope conductance of 19.9 +/- 1.8 pS (n = 7), and the reversal potential was near the resting potential of the atrioventricular node cell with 5.4 mM potassium chloride and 134.6 mM sodium chloride in the pipette. The channel was passing mainly potassium ions, but sodium ions also seemed to carry a fraction of the current. The possible role of the transient outward current in the quiescent node cell is discussed.

Cardiac atrioventricular junctional tissues in hearts from infants who died suddenly

The cause of sudden infant death syndrome is not known at present. Most agree that in the majority of cases it involves primary apnea. However, cardiac abnormalities probably account for a subset of these deaths. An investigation into the structure of the atrioventricular (AV) junctional tissues of the heart would provide insight into the frequency of sudden death in infants that might result from abnormal cardiac morphology. The hearts of seven infants who died from diagnosed sudden infant death syndrome were examined by serially sectioning and studying this critical region of the heart. The hearts of these infants could be divided into three groups on the basis of their morphologic features. In the first group, represented by two cases, there were marked variations from normal, the most striking feature being the presence of accessory pathways. In the second group, represented by four cases, the AV junctional tissues were not fully mature and clusters of AV nodal and bundle cells were dispersed throughout the anulus fibrosus. In the third group, the structure of the junctional tissues was normal. There remains a distinct subset of infants who might have died suddenly and unexpectedly from cardiac abnormalities that needs to be more completely defined.

Adenosine-5'-triphosphate-sensitive single potassium channel in the atrioventricular node cell of the rabbit heart.

The patch-clamp method was applied to single atrioventricular (a.v.) node cells of the rabbit heart to study the characteristics of the K+ channel. When the electrode contained 5.4 mM-K+, depolarizations of the cell-attached patch membrane induced outward single channel currents characterized by burst-like openings; the open-state probability increased from 0.005-0.01 at -40 mV to 0.07-0.1 at +20 mV of membrane potential. The reversal potentials of the current at K+ concentrations of 5.4, 20 and 130 mM in the electrode agreed with those given by the Nernst equation, indicating that this channel is selective for K+ ions. The slope conductance of the channel decreased beyond 60-90 mV positive to the reversal potential (inward-going rectification). The conductance near the reversal potential increased with increasing K+ concentrations on either side of the membrane: from 31-32 pS at 5.4 mM-K+ to 41-42 pS at 20 mM-K+ on the outside, and from 19 pS at 90 mM-K+ to 29.3 pS at 130 mM-K+ on the inside. Superfusion of the cell with 5.4 mM-CN-, glucose-free Tyrode markedly increased the number of channel openings in the cell-attached patch. In the inside-out patch, application of 1 mM-adenosine-5'-triphosphate (ATP) at the inner surface of the patch membrane blocked reversibly the channel activity, while 1 mM-adenosine-5'-diphosphate (ADP) failed to block it. The conductance and kinetics of the channel were not modified by increasing the Ca2+ concentration from 10(-8) M to 5 X 10(-6) M on the inner side of the membrane, while a further increase in Ca2+ to 10(-4) M decreased the open-state probability. The probability density for the open time fitted well with an exponential distribution (time constant of 5.4 ms at 60 mV positive to the resting potential), while that for the closed time was separated into a fast and a slow component (time constants of 4.0 and 132.0 ms, respectively). The time constant of the slow component decreased significantly with depolarization in some preparations. However, neither the time constant of the fast component of the closed-time histogram nor that of the open-time histogram was voltage-dependent.

Resting K conductances in pacemaker and non-pacemaker heart cells of the rabbit.

Currents through the inward rectifier K channel (iK X rec) and the ACh-operated K channel (iK X ACh) were recorded in isolated heart cells of rabbit using the patch clamp technique with electrodes having 0.5-1 micron tip inner diameter. The maximum number of overlaps of open iK X rec channels per patch was measured over 347 experiments. An average of 2.3 was found in ventricular cells and 0.03-0.06 in sinoatrial (S-A) and atrioventricular (A-V) node cells. The estimated total number of the iK X rec channels for each ventricular cell was great enough to supply the resting K conductance of the cell. The iK X ACh channel was present in S-A and A-V node cells, but was never observed in the ventricular cells. The resting conductance of the nodal cells measured with whole cell clamp recordings was about 16 times smaller than that of the ventricular cells, and was hardly decreased at all by the removal of K+ from the bath solution. Thus, the lower membrane potential of the nodal cells compared with that of the ventricular cells was attributed to the smaller K conductance of the resting membrane, which is due to the very low density of the iK X rec channel. On the other hand, the iK X ACh channel, when activated by neural regulation, may play a major role in generating the resting K conductance of the nodal cells.

Effects of managanese ions and diltiazem on the spontaneous action potential of the canine atrio-ventricular node cell

Effects of Mn 2+ (10 −4 to 10 −3 m) and diltiazem (10 −7 to 10 −6 m) on the spontaneous action potential were studied in small preparations of the canine atrio-ventricular (A-V) node. Mn 2+ and diltiazem decreased the maximum rate of rise ( V ̇ max ), amplitude of the action potential and rate of depolarization of the slow diastolic depolarization in a concentration-dependent manner. The spontaneous action potentials were depressed by the drugs, and were changed into abortive action potentials. Decrease in the rate of depolarization of the slow diastolic potential was much more prominent with Mn 2+ than with diltiazem. These results indicate that the slow inward current may not play an important role in the initiation of the slow diastolic depolarization of the A-V node cell.

Differentiation of the atrioventricular node, the atrioventricular bundle and the bundle branches in the bovine heart: an immunohistochemical and enzyme histochemical study.

The previous observations of differences between different cardiac regions (ventricular myocardium, atrial myocardium, Purkinje fibre system) with respect to the maturation of the M-line region and the establishment of mature metabolic characteristics, have been extended. It was found that M-line maturation proceeds differently also between different regions of the conduction system. The M-line proteins, myomesin and MM-creatine kinase, were detected earlier, by means of immunohistochemistry, in the AV bundle and bundle branch cells than in the AV node cells. Also, a difference was observed in large foetuses. Striations in the AV node were less evident than in the AV bundle and the bundle branches in sections incubated with antibodies against myomesin as well as against MM-creatine kinase. Using enzyme histochemistry it was observed that the differences in metabolic properties between the AV node, the AV bundle and the bundle branches on the one hand, and the ordinary myocardium on the other, of adult hearts, are not established at the early stages. No clear difference in activity of succinate dehydrogenase was seen between the conduction tissues and the ordinary myocardium in the foetal hearts, while the conduction tissues showed a lower activity in the adult hearts. Furthermore, the pattern of activity of mitochondrial glycerol-3-phosphate dehydrogenase between the conduction tissues and the atrial and ventricular myocardium was quite different in early foetal stages compared with the adult stage.

The early development of the AV node and bundle in the ferret heart.

The development of the atrioventricular (AV) junctional tissues in the ferret embryonic heart was studied on days 16, 18, and 21 of gestation. This important region of the heart was examined with PAS and toluidine-blue staining at the light microscope level and with transmission electron microscopy at the ultrastructural level. By day 16 of gestation the ferret heart was in the initial stages of convolution. The heart was at the primitive four-chamber stage by 18 days postcoitum. On day 21 of gestation the heart was in the process of being septated. The AV nodal primordia were first observed as two clusters of cells in the dorsal wall of the common atrium of the 16 day ferret embryo heart. These nodal primordial cells were morphologically different from working myocardial cells or cells of the AV canal. The AV canal cells were particularly numerous in the dorsal wall of the canal and eventually gave rise to the AV bundle in this region. On day 18 of gestation the morphological differences between the AV nodal, AV canal, and myocardial cells were readily apparent. By 21 days postcoitum, the AV node with its two regions had reached its definitive anatomic position. The AV bundle was also present in its normal adult location. The AV nodal cells were distinctly different when compared to the ventricular or atrial myocytes at this stage in development. In addition, the AV bundle cells were morphologically different from the AV nodal cells and working myocardial cells. A discussion of these findings relates this information to current descriptions of how the AV node and bundle develop.

Intracellular potassium activity in rabbit sinoatrial node. Evaluation during spontaneous activity and arrest.

HomeCirculation ResearchVol. 51, No. 3Intracellular potassium activity in rabbit sinoatrial node. Evaluation during spontaneous activity and arrest. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBIntracellular potassium activity in rabbit sinoatrial node. Evaluation during spontaneous activity and arrest. A O Grant and H C Strauss A O GrantA O Grant Search for more papers by this author and H C StraussH C Strauss Search for more papers by this author Originally published1 Sep 1982https://doi.org/10.1161/01.RES.51.3.271Circulation Research. 1982;51:271–279 Previous Back to top Next FiguresReferencesRelatedDetailsCited By Shi W and Zhou M Optimal Single-Pulse for Pacemakers Based on a Sinoatrial Model, IEEE/ASME Transactions on Mechatronics, 10.1109/TMECH.2011.2176745, 18:1, (348-354) Opthof T (1988) The mammalian sinoatrial node, Cardiovascular Drugs and Therapy, 10.1007/BF02125744, 1:6, (573-597), Online publication date: 1-Mar-1988. Irisawa H (1987) Membrane currents in cardiac pacemaker tissue, Experientia, 10.1007/BF01945510, 43:11-12, (1131-1135), Online publication date: 1-Dec-1987. Campbell T (2012) Differing electrophysiological effects of class IA, IB and IC antiarrhythmic drugs on guinea-pig sinoatrial node, British Journal of Pharmacology, 10.1111/j.1476-5381.1987.tb10294.x, 91:2, (395-401), Online publication date: 1-Jun-1987. Molyvdas P and Sperelakis N (2012) Effects of calcium antagonistic drugs on the electrical activity of rabbit sino-atrial node, British Journal of Pharmacology, 10.1111/j.1476-5381.1986.tb09493.x, 88:1, (249-258), Online publication date: 1-May-1986. (1997) Threshold effects of acetylcholine on primary pacemaker cells of the rabbit sino-atrial node, Proceedings of the Royal Society of London. Series B. Biological Sciences, 10.1098/rspb.1985.0006, 223:1232, (355-378), Online publication date: 22-Jan-1985. Nakayama T and Irisawa H (1985) Transient outward current carried by potassium and sodium in quiescent atrioventricular node cells of rabbits., Circulation Research, 57:1, (65-73), Online publication date: 1-Jul-1985. Molyvdas P and Sperelakis N (1984) Effects of Calcium Antagonistic Drugs on Various Heart Tissues, Including Blockade of the Slow Channels and Depression of Postdrive Hyperpolarization. Calcium Antagonists, 10.1007/978-1-4613-3810-9_12, (153-178), . Sperelakis N (1984) Effects of Calcium Slow Channel Blockers on the Slow Action Potentials of Cardiac Muscle and Vascular Smooth Muscle Calcium Antagonists, 10.1007/978-1-4613-3810-9_3, (21-45), . Baumgarten C, Singer D and Fozzard H (1984) Intra- and extracellular potassium activities, acetylcholine and resting potential in guinea pig atria., Circulation Research, 54:1, (65-73), Online publication date: 1-Jan-1984. September 1, 1982Vol 51, Issue 3 Advertisement Article InformationMetrics Copyright © 1982 by American Heart Associationhttps://doi.org/10.1161/01.RES.51.3.271 Originally publishedSeptember 1, 1982 PDF download Advertisement

Structure and function of specific regions in the canine atrioventricular node.

The functional subregions of the rabbit atrioventricular (AV) node have been examined in detail, but it has not been possible to subject the normal canine AV node to such rigorous scrutiny. Arterial perfusion and beveled microelectrodes have now allowed us to explore the anatomic and functional regions of the isolated canine AV node. The atria and AV junctional tissues of 20 young dogs were excised and selectively perfused with physiological solution through the nutrient arteries to the sinus node, AV node, and His bundle. AV node action potentials had shapes similar to those of the rabbit AV node and were conducted slowly (56 +/- 7 mm/s); slowest conduction (16 +/- 14 mm/s) was observed in the distal AV node where diastolic depolarization was always recorded and where maximum upstroke velocity of the action potential was slowest. From subsequent anatomic studies of the same preparations we found that the proximal region of the canine AV node was predominantly composed of interwoven slender transitional cells and that the distal region contained bundles of transitional cells and small but conspicuous aggregations of P-cells. The proximal portion of the canine AV node appeared to be organized for triage of atrial input during sinus rhythm. Electron microscopic examinations revealed numerous relatively long (greater than 1.0 micrometers) gap junctions between proximal AV node cells. The large gap junctions may provide an anatomic basis for electrotonic interaction during summation and conduction of AV node inputs. The distal AV node is the site of slowest AV conduction and also where most forms of AV junctional rhythm originate.

Fine structural identification of individual cells subjected to microelectrode recording in perfused cardiac preparations

We recorded transmembrane potentials from atrial, AV nodal and ventricular cells in perfused canine and rabbit heart preparations, and from Purkinje cells in superfused canine false tendons. Recording was maintained during perfusion with an aldehyde fixative. Action potential duration was greatly prolonged, and finally repolarization failed when the cells became fixed. After fixation the microelectrodes were withdrawn. Appropriate tissue blocks were embedded in Epon and serially sectioned at 4 μm. In 24 out of 34 attempts, the very cell recorded from was identified under the light microscope. After remounting and resectioning of the 4 μm sections for electron microscopy, the terminal electrode track was found in 12 instances, the very end of the track in six cases. Two main types of atrial action potentials were recorded: with and without a plateau phase. After retrieval of the individual cells we found no basis for a morphological distinction between different cell types. In the AV node, electrotonic contact between two cells was established for distances up to 320 μm by delivering current pulses to one of two microelectrodes which were simultaneously in an intracellular position. Both “N” and “NH” types of action potentials could originate in the proximal atrioventricular bundle. Possibly the N-type in this location was induced by hypoxia. Impalements of Purkinje fibres and ventricular myocardial cells extended the observations on details of microelectrode penetration and impalement damage. The most conspicuous disorder observed in all cells impaled by a microelectrode was a local or universal hypercontraction of myofibrils. In all cases where stable recordings were obtained, the microelectrode tip was found close to the cell membrane opposite to the site of entrance.

Single K channels activated by acetylcholine (ACh) in isolated AV nodal cells

Single K channels activated by acetylcholine (ACh) in isolated AV nodal cells

The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells.

Ventricular and atrioventricular nodal cells from guinea pig and rabbit hearts were isolated by perfusing the heart with collagenase (Langendorff perfusion). In these cells the cyclic nucleotides cAMP and cGMP or Ca and EGTA were injected through a microelectrode by pressure (0.5-3 kg/cm2). The effect of injection on both the action potential and the hyperpolarization induced by acetylcholine was studied. The following results were obtained. 1. cAMP prolonged the ventricular action potential and shifted the plateau to more positive potentials. The configuration of the A-V nodal action potential was not detectably changed by cAMP injection, but the spontaneous rate was increased. 2. cGMP first shortened the ventricular action potential. In most experiments this effect was followed by long lasting prolongation of the action potential. 3. Both extracellular and intracellular application of dibutyryl cGMP shortened the ventricular action potential but did not produce a subsequent prolongation. However, prolongation was observed on injection of GMP, the direct metabolite. 4. Injection of cGMP in nodal cells did not hyperpolarize the membrane nor slow the spontaneous rate; rather, an increase in rate was observed. 5. The acetylcholine-induced hyperpolarization was not altered in amplitude or time course by the injection of cAMP, cGMP, Ca or EGTA. 6. The results support the hypothesis that cGMP might be involved in the control of voltage-controlled ionic channels but suggest that it does not play a role as a mediator of the classical muscarinic action i.e. the activation of a specific potassium channel by acetylcholine.

The ultrastructure of the atrioventricular junctional tissues in the newborn ferret heart.

In this study the structure of the atrioventricular (AV) node and bundle in the newborn ferret heart was examined by light and electron microscopy. At the light microscopic level the AV node could be subdivided into deep and superficial portions. Electron microscopy revealed that both superficial and deep AV nodal cells were characterized by a paucity of myofibrils, desmosomes, fasciae adherentes and gap junctions. Deep V nodal cells, however, had more surface specializations than did superficial AV nodal cells. In both subdivisions the constituent cells were ellipsoid with tapering end-processes. In contrast to the nodal cells, the newborn AV bundle cells were round to ovoid. The AV bundle cells were organized into large fascicles, and there was a high frequency of anastomosing intercommunication between fascicles. These bundle cells had few myofibrils and high incidence of apposed plasma membrane. The present morphological findings support the concept that there are significant postnatal morphological changes that occur in the region of the AV junction. These results are also consistent with findings in other species that AV nodal conduction time is similar in newborns and adults, while conduction through the AV bundle increases with age.