Gap Junction Channels and Cardiac Impulse Propagation

The role of gap junction channels on cardiac impulse propagation is complex. This review focuses on the differential expression of connexins in the heart and the biophysical properties of gap junction channels under normal and disease conditions. Structural determinants of impulse propagation have been gained from biochemical and immunocytochemical studies performed on tissue extracts and intact cardiac tissue. These have defined the distinctive connexin coexpression patterns and relative levels in different cardiac tissues. Functional determinants of impulse propagation have emerged from electrophysiological experiments carried out on cell pairs. The static properties (channel number and conductance) limit the current flow between adjacent cardiomyocytes and thus set the basic conduction velocity. The dynamic properties (voltage-sensitive gating and kinetics of channels) are responsible for a modulation of the conduction velocity during propagated action potentials. The effect is moderate and depends on the type of Cx and channel. For homomeric-homotypic channels, the influence is small to medium; for homomeric-heterotypic channels, it is medium to strong. Since no data are currently available on heteromeric channels, their influence on impulse propagation is speculative. The modulation by gap junction channels is most prominent in tissues at the boundaries between cardiac tissues such as sinoatrial node-atrial muscle, atrioventricular node-His bundle, His bundle-bundle branch and Purkinje fibers-ventricular muscle. The data predict facilitation of orthodromic propagation.     

Impulse Origin and Propagation in a Bipolar Sensory Neuron

Intracellular recording techniques were used to study electrical activity in bipolar sensory cells associated with crayfish tactile receptors. Several lines of evidence indicate that spikes evoked by natural stimulation of the receptor originate at a dendritic locus. Although overshooting spikes are recorded in the soma in response to both natural and antidromic stimulation receptor potentials are observed only rarely, and, when present, their amplitude is less than 5 mv. Impulses propagating centrifugally into the soma following antidromic stimulation always exhibit an inflection in the rising phase of the spike; however, orthodromic spikes are usually uninflected. Occasionally, orthodromic responses (in the soma) exhibit rather unusual wave forms. Such spikes evoked by natural stimuli are indistinguishable from those elicited electrically in the dendrite, but they do not resemble antidromic impulses. Because the axonal and dendritic boundaries of the soma have a low safety factor for spike transmission, at high frequencies invasion of the soma by dendritic spikes is impeded and often blocked. The soma region can thus act as a low-pass filter. The significance of this self-limiting mechanism for the behavior of the animal is not known; it is suggested, however, that this impediment is a potentially critical one, and may, in other situations, have encouraged the evolution of alternative arrangements.     

The Effect of Membrane Parameters on the Properties of the Nerve Impulse

The effect of varying membrane capacitance, conductance, and rate constants on the properties of the nerve impulse is considered in terms of the degree of regeneration in the Hodgkin-Huxley model for the squid giant axon. It is shown through computer simulation that reducing regeneration generally increases the duration of the action potential and decreases its amplitude, rate of rise, and conduction velocity. The threshold becomes much less sharp and the amplitude of the response of a patch of membrane grades with stimulus strength. A second stimulus, applied shortly after a first stimulus, considerably perturbs the membrane potential from its original time-course. Under certain conditions, the nerve signal can propagate with a small decrement.     

Changes in Infrared Spectrum of Nerve during Excitation

MOLECULAR changes that occur in the membrane of nerve during depolarization are important to explain the mechanism of excitation and conduction. During an action potential in nerve the electrical field strength across the membrane undergoes a change of about 10⁵ V cm^?1 which could influence the conformation of membrane molecules possessing a flexible dipole¹. Several methods have been reported for detecting changes with excitation in nerve, muscle and electroplaque^2–11, but have been difficult to interpret. We have therefore used an adaptation of the method of modulation spectroscopy¹², which is based on changes in the absorption spectrum as a result of perturbing the molecular structure^13–16. Our method was based on absorption in the infrared, which occurs for molecular vibrations accompanied by changes in dipole moment.     

Impulse Propagation at the Septal and Commissural Junctions of Crayfish Lateral Giant Axons

Transmission across the septal junctions of the segmented giant axons of crayfish is accounted for quantitatively by a simple equivalent circuit. The septal membranes are passive, resistive components and transmission is ephaptic, by the electrotonic spread of the action current of the pre-septal spike. The electrotonic spread appears as a septal potential, considerably smaller than the pre-septal spike, but usually still large enough to initiate a new spike in the post-septal segments. The septal membranes do not exhibit rectification, at least over a range of ± 25 mv polarization and this accounts for their capacity for bidirectional transmission. The commissural branches, which are put forth by each lateral axon, make functional connections between the two axons. Transmission across these junctions can also be bidirectional and is probably also ephaptic. Under various conditions, the ladder-like network of cross-connections formed by the commissural junctions can give rise to circus propagation of impulses from one axon to the other. This can give rise to reverberatory activity of both axons at frequencies as high as 400/sec.     

Computation of Impulse Initiation and Saltatory Conduction in a Myelinated Nerve Fiber

A mathematical model of the electrical properties of a myelinated nerve fiber is given, consisting of the Hodgkin-Huxley ordinary differential equations to represent the membrane at the nodes of Ranvier, and a partial differential cable equation to represent the internodes. Digital computer solutions of these equations show an impulse arising at a stimulating electrode and being propagated away, approaching a constant velocity. Action potential curves plotted against distance show discontinuities in slope, proportional to the nodal action currents, at the nodes. Action potential curves plotted against time, at the nodes and in the internodes, show a marked difference in steepness of the rising phase, but little difference in peak height. These results and computed action current curves agree fairly accurately with published experimental data from frog and toad fibers.     

手掌分区与指掌侧总神经和指掌侧总动脉

目的：为研究手掌血管、神经损伤修复重建提供解剖学基础。方法：手掌借5条横平行线和4条纵平行线分为20区,解剖并观察指掌侧总神经和指掌侧总动脉在手掌的分布及其伴行关系。结果：第一、二指掌侧神经起始处位于7区外上象限,第三指掌侧总神经、小指尺掌侧神经起始处位于4区内下象限。第一、二、三指掌侧总动脉起始处位于7、8区近C线处。小指尺掌侧动脉起始处位于8区内下象限。第一、二指掌侧总神经在7区被掌浅弓骑跨,分弓上、下两段。弓上、下段,分别在13、14区D线处发出指掌侧固有神经。小指尺掌侧神经、第三指掌侧总神经起始处位于同名动脉的近侧,其行程在9、15、20区位于同名动脉的尺侧。第一、二指掌侧总动脉分别在18、19区距E线0．8-1．0cm处发出相应的指掌侧固有动脉。第一、二、三指掌侧总神经及其发出的指掌侧固有神经与同名的指掌侧总动脉的伴行关系有四型：H1、H2、O、V型。结论：指掌侧总神经与指掌侧总动脉在手掌的一定区域内有按规律分布的特点,有助于手掌损伤离断手术修复过程中指掌侧总神经与指掌侧总动脉的寻找和吻合,以及手掌神经阻滞麻醉的精确定位。     

Traveling Wave Solutions of a Nerve Conduction Equation

We consider a pair of differential equations whose solutions exhibit the qualitative properties of nerve conduction, yet which are simple enough to be solved exactly and explicitly. The equations are of the FitzHugh-Nagumo type, with a piecewise linear nonlinearity, and they contain two parameters. All the pulse and periodic solutions, and their propagation speeds, are found for these equations, and the stability of the solutions is analyzed. For certain parameter values, there are two different pulse-shaped waves with different propagation speeds. The slower pulse is shown to be unstable and the faster one to be stable, confirming conjectures which have been made before for other nerve conduction equations. Two periodic waves, representing trains of propagated impulses, are also found for each period greater than some minimum which depends on the parameters. The slower train is unstable and the faster one is usually stable, although in some cases both are unstable.     

Landscape Excitation Profiles and Excess Thermodynamic Properties of Disaccharide Aqueous Solutions

We will consider the use of the bond model in characterizing, by the direct calculation route, the full excitation profile. The present work sets the temperature behaviour of the excessive value of some thermodynamic quantities, such as configurational entropy and heat capacity of two homologous disaccharide aqueous solutions. The findings represent important data for understanding the better lyoprotectant effectiveness of trehalose in comparison with sucrose.     

Evaluation of Excitation Propagation in the Rabbit Heart: Optical Mapping and Transmural Microelectrode Recordings

Background

Because of the optical features of heart tissue, optical and electrical action potentials are only moderately associated, especially when near-infrared dyes are used in optical mapping (OM) studies.

Objective

By simultaneously recording transmural electrical action potentials (APs) and optical action potentials (OAPs), we aimed to evaluate the contributions of both electrical and optical influences to the shape of the OAP upstroke.

Methods and Results

A standard glass microelectrode and OM, using an near-infrared fluorescent dye (di-4-ANBDQBS), were used to simultaneously record transmural APs and OAPs in a Langendorff-perfused rabbit heart during atrial, endocardial, and epicardial pacing. The actual profile of the transmural AP upstroke across the LV wall, together with the OAP upstroke, allowed for calculations of the probing-depth constant (k ~2.1 mm, n = 24) of the fluorescence measurements. In addition, the transmural AP recordings aided the quantitative evaluation of the influences of depth-weighted and lateral-scattering components on the OAP upstroke. These components correspond to the components of the propagating electrical wave that are transmural and parallel to the epicardium. The calculated mean values for the depth-weighted and lateral-scattering components, whose sum comprises the OAP upstroke, were (in ms) 10.18 ± 0.62 and 0.0 ± 0.56 for atrial stimulation, 9.37 ± 1.12 and 3.01 ± 1.30 for endocardial stimulation, and 6.09 ± 0.79 and 8.16 ± 0.98 for epicardial stimulation; (n = 8 for each). For this dye, 90% of the collected fluorescence originated up to 4.83 ± 0.18 mm (n = 24) from the epicardium.

Conclusions

The co-registration of OM and transmural microelectrode APs enabled the probing depth of fluorescence measurements to be calculated and the OAP upstroke to be divided into two components (depth-weighted and lateral-scattering), and it also allowed the relative strengths of their effects on the shape of the OAP upstroke to be evaluated.     

On Propagation of Excitation Waves in Moving Media: The FitzHugh-Nagumo Model

Background

Existence of flows and convection is an essential and integral feature of many excitable media with wave propagation modes, such as blood coagulation or bioreactors.

Methods/Results

Here, propagation of two-dimensional waves is studied in parabolic channel flow of excitable medium of the FitzHugh-Nagumo type. Even if the stream velocity is hundreds of times higher that the wave velocity in motionless medium (), steady propagation of an excitation wave is eventually established. At high stream velocities, the wave does not span the channel from wall to wall, forming isolated excited regions, which we called “restrictons”. They are especially easy to observe when the model parameters are close to critical ones, at which waves disappear in still medium. In the subcritical region of parameters, a sufficiently fast stream can result in the survival of excitation moving, as a rule, in the form of “restrictons”. For downstream excitation waves, the axial portion of the channel is the most important one in determining their behavior. For upstream waves, the most important region of the channel is the near-wall boundary layers. The roles of transversal diffusion, and of approximate similarity with respect to stream velocity are discussed.

Conclusions

These findings clarify mechanisms of wave propagation and survival in flow.     

Somatotopy of Digital Nerve Projections to the Dorsal Horn in the Monkey

The dorsal horn projection patterns of finger nerves were investigated in four Macaca mulatto monkeys. Proper digital branches of the median nerves, serving the radial aspect of a digit on each hand, were loaded with wheatgerm agglutinin—horseradish peroxidase complex (WGA:HRP). The distribution of the lectin—enzyme complex was mapped in the right and left dorsal horns.

The dorsal horn projections of the digital nerves were localized in segments C₆-C₈ in laminae I-VI, primarily in laminae I-IV. The wedge-shaped termination zones were somatotopically organized, in agreement with the projections of the digits in cats. The fingers are represented medially, as they are in the cat. This similarity suggests that there is a mediolateral gradient of dorsal horn organization similar to that of the cat, with distal skin represented medially and proximal skin represented laterally. The rostrocaudal trajectory of finger representation, with digit 1 most rostral and digit 5 most caudal, is also in agreement with the organization of hindlimb toe projections in the cat. There was a high degree of bilateral symmetry for homologous nerves, and little overlap of projections from nerves innervating adjacent fingers. The sample size was too small to permit us to assess interanimal variation. These results suggest a similar somatotopy of projections, and presumably of dorsal horn cell somatotopy, in monkey and cat.     

Computer Solutions for Photosynthesis Rates from a Two Pigment Model

A kinetic model for a two pigment mechanism of photosynthesis based on observations made on the red alga Porphyridium cruentum is developed. The model supposes that different products are formed by chlorophyll and phycobilin pigments and that these products react to produce oxygen. The product of the chlorophyll reaction is also rapidly utilized for O₂ consumption both in light and in the dark. Rate equations based on the model reactions were derived and put into an analog computer. The effect of varying parameters on the time course curves for oxygen exchange resulting from the model was studied. Appropriate selection of parameters yielded computer curves which resembled fairly closely the oxygen exchange curves obtained using Porphyridium. The model showed the Emerson enhancement effect, chromatic transients, “respiratory stimulation,” and other effects observed with live algae.     

Somatotopy of Digital Nerve Projections to the Cuneate Nucleus in the Monkey

Somatotopic arrangements of cells and fibers within the dorsal columns and the dorsal column nuclei have been mapped most precisely by electrophysiological recording methods. This study uses an anatomical approach to evaluate the precision of individual digital nerve projections to the cuneate nucleus (CN) in young macaque monkeys. Digital nerves supplying about one-half the palmar skin of a digit were surgically exposed, cut, and treated with wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) on 3 successive days. After 2 additional days, animals were killed and medullas were recovered for study of serial sections reacted to display axons labeled by transganglionic transport of label. Labeled afferent fibers from each digit were found within a circumscribed columnar zone extending through the caudal CN and rostrally throughout the pars rotunda of CN. At caudal levels, diffuse projections reach the dorsal edge of the CN; more rostrally, they shift into deeper parts of the nucleus and are heaviest along its ventral and medial edges at levels near the obex. Fibers from the thumb (digit 1) project lateral (and ventral) to those from digit 2, and projections from digit 3 are medial to those from 2. Each digital projection field is closely adjacent to that from the adjacent digit. Few fibers extend to the rostral CN. Projection fields of homologous digits are quite symmetrical on the two sides. Although there do seem to be some differences in the somatotopic arrangement of digital input in macaques compared to other nonprimate mammals studied previously, these observations (precisely organized, circumscribed fields for separate digits) define a system well designed for transmission of data encoding spatial relationships.     

A Mechanism for Nerve Cell Excitation by Norepinephrine via Alpha-1 Adrenoceptors: Inhibition of Potassium M-Current

Some of the excitatory effects of norepinephrine on central neurons are mediated by alpha-1 (α1) adrenoceptors. These receptors are coupled to the Gq family of G proteins, and hence stimulate hydrolysis of the membrane phospholipid phosphatidylinositol-4,5-bisphosphate. Other receptors of this type can excite neurons by inhibiting the subthreshold voltage-gated potassium M-current. We tested this possibility using rat sympathetic neurons transformed to express α1a receptors. The α1 agonist phenylephrine strongly inhibited the M-current recorded under voltage-clamp by 72 ± 11 % (n = 4) and in an unclamped neuron dramatically increased the number of action potentials produced by a 2 s depolarizing current step from 2 to 40, without effect on control neurons devoid of α1 receptors. We suggest that this might be a potential cause of the increased excitability produced by norepinephrine in some central neurons.