On reversible changes in the steady state ion-conductance of the Ranvier node membrane under low frequency sound fields

Summary The influence of sound waves on the stationary membrane conductivity of the axon membrane in myelinated nerve was investigated. Sound fields with frequencies within the auditory limit shift the transition voltage V_tr and correspondingly the threshold voltage of the action potential in polarisation direction. The results indicate that these changes of the electrical membrane behavior are due to a direct mechanical interaction between low frequency sound fields and membrane structure.     

Resting potential of excitable neuroblastoma cells in weak magnetic fields

The mechanism by which static and low-frequency magnetic fields are transduced into biological signals responsible for reported effects on brain electrical activity is not yet ascertained. To test the hypothesis that fields can cause a subthreshold change in the resting membrane potential of excitable cells, we measured changes in transmembrane current under voltage clamp produced in SH-SY5Y neuroblastoma cells, using the patch-clamp method in the whole-cell configuration. In separate experiments, cells were exposed to static fields of 1, 5, and 75 G, to time-varying fields of 1 and 5 G, and to combined static and time-varying fields tuned for resonance of Na+, K+, Ca2+, or H+. To increase sensitivity, measurements were made on cells connected by gap junctions. For each cell, the effect of the field was evaluated on the basis of 100 trials consisting of a 5-s exposure immediately followed by a 5-s control period. In each experiment, the field had no discernible effect on the transmembrane current in the vicinity of zero current (- 50 mV voltage clamp). The sensitivity of the measuring system was such that we would have detected a current corresponding to a change in membrane potential as small as 38 microV. Consequently, if sensitivity of mammalian cells to magnetic fields is mediated by subthreshold changes in membrane potential, as in sensory transduction of sound, light, and other stimuli, then the ion channels responsible for the putative changes are probably present only in specialized sensory neurons or neuroepithelial cells. A change in transmembrane potential in response to magnetic fields is not a general property of excitable cells in culture.     

Dantrolene: evidence for effects on Na permeability properties of the nodal membrane

The effects of dantrolene on myelinated frog nerve fibers were studied in voltage clamp experiments. Dantrolene shifted the potential-dependent parameters describing Na+ permeability towards more negative membrane potentials. The findings are interpreted as a change in the negative surface charge of the membrane.     

Electro-mechanical noise in atrial muscle fibres of the carp

Summary Steady membrane voltage fluctuations have been observed in atrial muscle fibres of the carp. These voltage fluctuations produce minute mechanical oscillations, as revealed by an interference contrast microscope. The steady voltage fluctuations may be related to abnormal automaticity in the heart.Supported by the U.S. Israel Binational Science Foundation, Jerusalem, and is part of a thesis to be submitted by Ms Akselrod to the Tel-Aviv University. We thank Ms M. Bendikowski for her efficient technical assistance.     

Patch and whole-cell voltage clamp of single mammalian visceral and vascular smooth muscle cells

Dispersal of the constituent cells of mammalian visceral and vascular smooth muscles has permitted recordings both of membrane currents under whole-cell voltage clamp, and of currents through single ionic channels using the patch-clamp technique. A rectangular depolarizing step applied to a single cell under voltage clamp yielded a net inward current followed by a net outward current in normal physiological solution. In isolated, 'inside-out' patches of cell membrane a calcium- and potential-sensitive K channel (100 pS conductance) and a calcium-insensitive, potential-sensitive K+ channel (50 pS conductance) with slow kinetics have so far been identified and characterized.     

Time course of excitatory and inhibitory states of bulbar respiratory modulated neurons

Summary In respiratory modulated neurons of rabbits, vagally mediated inhibition is not bound to resting membrane potential oscillations. Latency of spinally evoked antidromical spike invasion, however, is shorter and threshold voltage is lower during the shift of membrane potential towards depolarization accompanying burst discharge.     

Ionic currents in morphogenesis

Morphogenetic fields must be generated by mechanisms based on known physical forces which include gravitational forces, mechanical forces, electrical forces, or some combination of these. While it is unrealistic to expect a single force, such as a voltage gradient, to be the sole cause of a morphogenetic event, spatial and temporal information about the electrical fields and ion concentration gradients in and around a cell or embryo undergoing morphogenesis can take us one step further toward understanding the entire morphogenetic mechanism. This is especially true because one of the handful of identified morphogens is Ca2+, an ion that will not only generate a current as it moves, but which is known to directly influence the plasma membrane's permeability to other ions, leading to other transcellular currents. It would be expected that movements of this morphogen across the plasma membrane might generate ionic currents and gradients of both electrical potential and intracellular concentration. Such ionic currents have been found to be integral components of the morphogenetic mechanism in some cases and only secondary components in other cases. My goal in this review is to discuss examples of both of these levels of involvement that have resulted from investigations conducted during the past several years, and to point to areas that are ripe for future investigation. This will include the history and theory of ionic current measurements, and a discussion of examples in both plant and animal systems in which ionic currents and intracellular concentration gradients are integral components of morphogenesis as well as cases in which they play only a secondary role. By far the strongest cases for a direct role of ionic currents in morphogenesis is the polarizing fucoid egg where the current is carried in part by Ca2+ and generates an intracellular concentration gradient of this ion that orients the outgrowth, and the insect follicle in which an intracellular voltage gradient is responsible for the polarized transport from nurse cell to oocyte. However, in most of the systems studied, the experiments to determine if the observed ionic currents are directly involved in the morphogenetic mechanism are yet to be done. Our experience with the fucoid egg and the fungal hypha of Achlya suggest that it is the change in the intracellular ion concentration resulting from the ionic current that is critical for morphogenesis.     

Ionic currents in morphogenesis

Summary Morphogenetic fields must be generated by mechanisms based on known physical forces which include gravitational forces, mechanical forces, electrical forces, or some combination of these. While it is unrealistic to expect a single force, such as a voltage gradient, to be the sole cause of a morphogenetic event, spatial and temporal information about the electrical fields and ion concentration gradients in and around a cell or embryo undergoing morphogenesis can take us one step further toward understanding the entire morphogenetic mechanism. This is especially true because one of the handful of identified morphogens is Ca²⁺, an ion that will not only generate a current as it moves, but which is known to directly influence the plasma membrane's permeability to other ions, leading to other transcellular currents. It would be expected that movements of this morphogen across the plasma membrane might generate ionic currents and gradients of both electrical potential and intracellular concentration. Such ionic currents have been found to be integral components of the morphogenetic mechanism in some cases and only secondary components in other cases. My goal in this review is to discuss examples of both of these levels of involvement that have resulted from investigations conducted during the past several years, and to point to areas that are ripe for future investigation. This will include the history and theory of ionic current measurements, and a discussion of examples in both plant and animal systems in which ionic currents and intracellular concentration gradients are integral components of morphogenesis as well as cases in which they play only a secondary role. By far the strongest cases for a direct role of ionic currents in morphogenesis is the polarizing fucoid egg where the current is carried in part by Ca²⁺ and generates an intracellular concentration gradient of this ion that orients the outgrowth, and the insect follicle in which an intracellular voltage gradient is responsible for the polarized transport from nurse cell to oocyte. However, in most of the systems studied, the experiments to determine if the observed ionic currents are directly involved in the morphogenetic mechanism are yet to be done. Our experience with the fucoid egg and the fungal hypha ofAchlya suggest that it is the change in the intracellular ion concentration resulting from the ionic current that is critical for morphogenesis.     

Role of neurotransmitter release and cyclic AMP-dependent membrane phosphorylation in low voltage myocardial automaticity

Low voltage myocardial automaticity (LVA) was investigated by pharmacological modulations of the presynaptic and postsynaptic processes. The sensitivity of LVA both to inhibitor and stimulator of neurotransmitter release suggests its involvement in LVA genesis. Moreover, LVA is blocked by the inhibition of the cyclic AMP system, supporting the participation of the c-AMP-dependent membrane phosphorylation in calcium-mediated cardiac electrogenesis.     

Structure of the gap junction channel and its implications for its biological functions

Gap junctions consist of arrays of intercellular channels composed of integral membrane proteins called connexin in vertebrates. Gap junction channels regulate the passage of ions and biological molecules between adjacent cells and, therefore, are critically important in many biological activities, including development, differentiation, neural activity, and immune response. Mutations in connexin genes are associated with several human diseases, such as neurodegenerative disease, skin disease, deafness, and developmental abnormalities. The activity of gap junction channels is regulated by the membrane voltage, intracellular microenvironment, interaction with other proteins, and phosphorylation. Each connexin channel has its own property for conductance and molecular permeability. A number of studies have tried to reveal the molecular architecture of the channel pore that should confer the connexin-specific permeability/selectivity properties and molecular basis for the gating and regulation. In this review, we give an overview of structural studies and describe the structural and functional relationship of gap junction channels.     

Patch and whole-cell voltage clamp of single mammalian visceral and vascular smooth muscle cells

Summary Dispersal of the constituent cells of mammalian visceral and vascular smooth muscles has permitted recordings both of membrane currents under whole-cell voltage clamp, and of currents through single ionic channels using the patch-clamp technique. A rectangular depolarizing step applied to a single cell under voltage clamp yielded a net inward current followed by a net outward current in normal physiological solution. In isolated, inside-out patches of cell membrane a calcium- and potential-sensitive K channel (100 pS conductance) and a calcium-insensitive, potential-sensitive K⁺ channel (50 pS conductance) with slow kinetics have so far been identified and characterized.     

聚氨酯材料在生物医学中的研究进展

聚氨酯是一种合成的高分子化合物,有较好的机械性能、高弹性和理想的生物相容性,被广泛地用于生物医学领域。本文综述了聚氨酯在凝胶材料、弹性体材料、膜材料以及抗菌材料等方面的研究现状及应用前景。     

Role of neurotransmitter release and cyclic AMP-dependent membrane phosphorylation in low voltage myocardial automaticity

Summary Low voltage myocardial automaticity (LVA) was investigated by pharmacological modulations of the presynaptic and postsynaptic processes. The sensitivity of LVA both to inhibitor and stimulator of neutrotransmitter release suggests its involvement in LVA genesis. Moreover, LVA is blocked by the inhibition of the cyclic AMP system, supporting the participation of the c-AMP-dependent membrane phosphorylation in calcium-mediated cardiac electrogenesis.Acknowledgment. The generous gift of RM1 12330A from Prof. G. Guellen, Paris, and of tolbutamide from Prof. T. Hayakawa, Tokyo, are gratefully acknowledged.     

Molecular mechanisms of BK channel activation

Large conductance, Ca²⁺-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological processes, such as muscle contraction, neural transmission and hearing. These physiological roles derive from the ability of BK channels to be synergistically activated by membrane voltage, intracellular Ca²⁺ and other ligands. Similar to voltage-gated K⁺ channels, BK channels possess a pore-gate domain (S5–S6 transmembrane segments) and a voltage-sensor domain (S1–S4). In addition, BK channels contain a large cytoplasmic C-terminal domain that serves as the primary ligand sensor. The voltage sensor and the ligand sensor allosterically control K⁺ flux through the pore-gate domain in response to various stimuli, thereby linking cellular metabolism and membrane excitability. This review summarizes the current understanding of these structural domains and their mutual interactions in voltage-, Ca²⁺ - and Mg²⁺ -dependent activation of the channel. Received 25 September 2008; received after revision 23 October 2008; accepted 24 October 2008     

Functional and structural determinants of reverse operation in the pH-dependent oligopeptide transporter PepT1

The functional and structural basis of reverse operation of PepT1 has been studied in Xenopus oocytes expressing the wild-type and mutated forms of this protein. Using brief pulses from a negative holding potential, wild-type and Arg282 mutants exhibit outward currents in the presence of Gly-Gln. The reversal potential of these currents is affected by both pH and substrate concentration, confirming coupled transport in the wild type and in the mutants as well. Long-lasting voltage and current-clamp experiments show that the outward currents are only temporary, and reflect accumulation and/or depletion effects near the membrane. The ability to operate in reverse mode was confirmed in all isoforms by intracellular injection of substrate. The role of Arg282 and Asp341 in the reverse transport was also investigated using charged substrates. Positive Lys-Gly (but not Gly-Lys) showed enhanced transport currents in the Arg282 mutants. In contrast, negative Gly-Asp and Asp-Gly elicited modest currents in all isoforms.     

Pictures of sounds: Wittgenstein on gramophone records and the logic of depiction

I consider the way Wittgenstein employed some kinds of sound recordings (but not others) in discussing logical form in the Tractatus logico-philosophicus. The year that Ludwig Wittgenstein was born in Vienna, 1889, nearby developments already underway portended two major changes of the coming century: the advent of controlled heavier than air flight and the mass production of musical sound recordings. Before they brought about major social changes, though, these innovations appeared in Europe in the form of children’s toys. Wittgenstein uses the fact that a symphony performance can be constructed from both a written musical score and the grooves of a gramophone record to explain what logical form is. His characterization of logical form in the Tractatus in terms of intertranslatability rather than in terms of interpretability is highlighted by reflecting on the kinds of examples of sound recordings that he did not use to illustrate the notion of logical form. There were other well known technologies for making visual records of sound at the time, but these did not serve to illustrate logical form.     

Electrophysiological study of interaural sound intensity difference in the dolphin Inia geoffrensis

A wave observed in the auditory brainstem responses (ABR), sensitive to the side of sound presentation, is described in a dolphin (Inia geoffrensis). Dependence of the wave threshold on location of the sound source showed that the interaural intensity difference was more than 20 dB.     

Instruments of Music,Instruments of Science: Hermann von Helmholtz's Musical Practices,his Classicism,and his Beethoven Sonata

The young Hermann Helmholtz, in an 1838 letter home, declared that he always appreciated music much more when he played it for himself. Though a frequent concert-goer, and celebrated for his highly influential 1863 work on the physiological basis of music theory, Die Lehre von den Tonempfindungen, it is likely that Helmholtz's enduring engagement with music began with his initial, personal experience of playing music for himself. I develop this idea, shifting the discussion of Helmholtz's work on sound sensation back to its origins, and examine the role of his material interaction with musical instruments and music itself. In his sound sensation studies, Helmholtz understood sound as an external, physical object. But Helmholtz also conceived of sound in musical terms. Further, Helmholtz's particular musical tastes as well as his deeply personal interaction with musical instruments allowed him to reconcile his conception of sound as physical object with his conception of sound as music. Helmholtz's physiological theory of sound sensation was both the product of and constitutive of how he heard and created sound. I argue that Helmholtz himself was the embodied reconciliation of his physiological theory of sound sensation and his belief that musical aesthetics were historically and culturally contingent.     

Electrophysiological study of interaural sound intensity difference in the dolphinInia geoffrensis

A wave observed in the auditory brainstem responses (ABR), sensitive to the side of sound presentation, is described in a dolphin (Inia geoffrensis). Dependence of the wave threshold on location of the sound source showed that the interaural intensity difference was more than 20 dB.     

Interaction between bradykinin and voltage-sensitive sodium channels in myelinated nerve fibers

The effects of externally and internally applied bradykinin on the excitability of single myelinated nerve fibers were studied. External bradykinin (10 microM) slightly prolongs the action potential of a single myelinated nerve fiber; hence, when the fibers are stimulated by long-lasting pulses, this raises the frequency of repetitive firing in sensory fibers and evokes repetitive activity in motor fibers. Under voltage-clamp conditions, sodium channel inactivation is slowed, while sodium channel activation remains unaffected. Prolonged depolarization of the membrane leads to a maintained sodium current. The voltage dependence of the steady-state sodium current inactivation (h infinity) is shifted in the depolarized direction by approximately 10 mV. Internally applied bradykinin produces a frequency-dependent block of the sodium current. The phenomena described here imply that more than one site on the sodium channel is modified by bradykinin.