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H M Fishman

Publications and source records attributed to H M Fishman.

53 records · Page 3Linked to original sources
PubMed1975

Noise measurements in squid axon membrane.

A small area (10(-4) to 10(-5) cm2 patch) of the external surface of a squid (Loligo pealei) axon was "isolated" electrically by means of a pair of concentric glass pipettes and sucrose solution to achieve a low extraneous noise measurement of spontaneous fluctuations in membrane potential and current. The measured "small-signal" impedance function of the isolated patch in seawater was constant at low frequencies and declined monotonically at frequencies beyond 100Hz. It is shown that the power-density spectrum (PDS) of voltage noise, which generally reflects the current-noise spectrum filtered by the membrane impedance function, is equivalent to the power spectrum of current-noise up to frequencies where the impedance decline is significant (Fishman, 1973a, Proc. Nat. Acad. Sci. USA 70:876). This result is in contrast to an impedance resonance measured under uniform constant-current (internal axial wire) conditions, for which the voltage-noise PDS reflects the impedance resonance. The overdamped resonance in the patch technique is a consequence of the relatively low resistance (1 Momega) pathways through the sucrose solution in the interstitial Schwann cell space which surround and shunt the high resistance (10-100 Momega) membrane patch. Current-noise measurements during patch voltage clamp extend observation of patch ion-conductance fluctuations to 1 kHz. Various tests are presented to demonstrate the temporal and spatial adequacey of patch potential control during current-noise measurements.

Animals↗
PubMed1975

Potassium-ion conduction noise in squid axon membrane.

Spectral analysis (1-1000 Hz) of spontaneous fluctuations of potential and current in small areas of squid (Loligo pealei) axon shows two forms of noise: f-1 noise occurs in both excitable and inexcitable axons with an intensity which depends upon the driving force for potassium ions. The other noise has a spectral form corresponding to a relaxation process, i.e. its asymptotic behavior at low frequencies is constant, and at high frequencies it declines with a slope of -2. This latter noise occurs only in excitable axons and was identified in spectra by (1) its disappearance after reduction of K+ current by internal perfusion with solutions containing tetraethylammonium (TEA+), Cs+ or reduced [Ki+] and (2) its insensitivity to block of Na+ conduction and active transport. The transition frequency of relaxation spectra are also voltage and temperature dependent and relate to the kinetics of K+-conduction in the Hodgkin-Huxley formulation. These data strongly suggest that the relaxation noise component arises from the kinetic properties of K+ channels. The f-1 noise is attributed to restricted diffusion in conducting K+ channels and/or leakage pathways. In addition, an induced K+ conduction noise associated with the binding of TEA+ and triethyldecylammonium ion to membrane sites is described. Measurement of the induced noise may provide an alternative means of characterizing the kinetics of interaction of these molecules with the membrane and also suggests that these and other pharmacological agents may not be useful in identifying noise components related to the sodium conduction mechanism which, in these experiments, appears to be much lower in intensity than either the normal K conduction or induced noise components.

Animals↗
PubMed1975

Excess electrical noise during current flow through porous membranes separating ionic solutions.

Spectral analysis of electrical noise from various artificial membrane systems suggests that excess noise of an f-n spectral form, where n is approximately unity, is not primarily a bulk phenomenon simply dependent on the number of charge carriers. Measurements from aqueous and nonaqueous electrolytic resistors, comprised of several different ionic species, show only flat power density spectra under applied currents, even at extreme dilutions. Excess noise of f-n form is observed under applied d-c current in single pore membranes, as previously reported, but is also seen in multipore and polymer mesh membranes. Calculations based on single pore membrane noise data are in significant variance with the bulk charge carrier model proposed by Hooge. These observations suggest that such excess noise occurs in conjunction with anisotropic constraints to ion flow.

Collodion↗
PubMed1975

Noise measurements in axon membranes.

A fluctuation (noise) component, which arises from spontaneous microscopic conductance perturbations, about the mean conduction characteristics of small areas of axon membrane has been measured and appears to relate to voltage-dependent potassium-ion movements. Since the kinetics of relaxing membrane structures which produce ion permeation noise may be deduced from the form of power density spectra of fluctuations, a comparison of measured and theoretical noise spectra may lead to direct tests of conduction of models.

Animals↗
PubMed1973

Relaxation spectra of potassium channel noise from squid axon membranes.

Power density spectra of electrical fluctuations in potential and current (during voltage clamp) in the steady state, measured from electrically isolated patches of squid axon membrane, contain a noise component that is of the form [1 + (f/f(c))(2)](-1). For potential and temperature changes f(c) = (2pitau(n))(-1), where tau(n) is the Hodgkin-Huxley relaxation time for the potassium channel. These and other data strongly suggest that this noise is due to the potassium ion passage process in the membrane. Furthermore, by comparison of the values of f(c) from relaxation spectra of membrane channel noise with those from calculated (Hodgkin-Huxley equations) power spectra, it is possible to relate and compare channel models that previously could only be applied to macroscopic potassium conductance data. An initial result of this comparison suggests that a two-state (open-closed) conductance model, which is based upon a literal interpretation of the Hodgkin-Huxley equations, is not likely to be correct.

Animals↗
PubMed1970

Direct and rapid description of the individual ionic currents of squid axon membrane by ramp potential control.

Computations based upon the Hodgkin-Huxley equations and experimental data from squid axons show that ramp functions can be used as commands to a voltage clamp system to selectively observe either the fast (sodium) or slow (potassium) process in axon membranes without chemical separation techniques or computer assistance. Each process is characterized directly (on line) and rapidly (real time) by generating a current-potential curve on an oscilloscope for fast or slow rates of change of membrane potential (ramps). The speed and directness of this method of characterizing each of the essential axonal events permit quantitative measurement of the kinetics of rapid effects on these processes due to various pharmacological agents such as tetrodotoxin and tetraethylammonium ion or other experimental changes in the membrane environment.

Animals↗
PubMed1969

The N-shaped current-potential characteristic in frog skin. I. Time development during step voltage clamp.

A fast (10 musec) voltage-clamp system similar to that used on nerve axons was applied across the frog skin. An electrical analog is used to obtain the electrical parameters and to estimate the time (300 musec) required to voltage clamp the excitable membrane layer in the skin. The speed of the clamp allows observation of the early development in time of an N-shaped current-potential (I-V) relation. The isochronal I-V curves constructed from step clamp data show the beginning of a negative slope in about 250 musec after successively applied step changes in skin potential (> 200 mv). Subsequently, the negative slope reaches a quasi-steady state interval (0.4-1.5 msec) and then decays and disappears in the next 20 msec. The negative slope I-V characteristic is only found in skins which exhibit spike generation under current clamp.

Animals↗
PubMed1969

The N-shaped current-potential characteristic in frog skin. II. Kinetic behavior during ramp voltage clamp.

Previous step voltage-clamp measurements on frog skin showed the presence of an N-shaped current-potential (I-V) relation in excitable skin. However, the collection and reconstruction of I-V data using discrete step changes of skin potential was tedious because of the long refractory period (up to 1 min) in frog skin. A direct and rapid (5 msec) method for recording the N-shaped I-V characteristic in real time is presented. Ramp functions are used as the command to the clamp system instead of a step function. Consequently the skin potential is forced to change in a linear manner (as commanded) and the skin current can be recorded as a continuous function of the controlled change of skin potential. With the ramp clamp, a low-resistance membrane state ( 10 Omega . cm(2)) resembling a breakdown phenomenon was observed at high skin potential ( 300 mv). Entry into the low resistance state resulted in a collapse of the N-shaped I-V relation to a nearly linear function. The utility of the ramp measurement is demonstrated by predicting (1) that the maximum rate of rise of the spike occurs at a voltage corresponding to the valley (local minimum) in the N-shaped I-V curve, (2) that the rate of rise of the spike increases with increasing clamp currents, (3) the voltage peak of the spike, and (4) the time course of the rising phase of the spike.

Animals↗
PubMed1969

The N-shaped current-potential characteristic in frog skin. 3. Ionic dependence.

A ramp voltage clamp measurement described previously is used to detect alterations in the frog skin current-potential (I-V) characteristic following removal or replacement of various ions in the solutions bathing the skin. The ionic requirements for the maintenance of a negative-slope I-V property are the following: Ca(++), Na(+), and Cl(-) must be in the outside solution; K(+) and Cl(-) must be in the inside solution. Removal of any one of these ions from its respective solution results in the decay and eventual disappearance of the negative slope.The similarity between the I-V characteristic following Ca(++) removal with EDTA from the outside solution and the I-V relation in a refractory skin suggests that the loss (refractory state) and recovery of the negative slope is a consequence of unbinding and subsequent rebinding of Ca(++) to membrane sites. The role of the univalent ions is not clear-presumably some or all of these ions constitute the current through the skin; however, some of these ions may also be involved in maintaining a membrane condition necessary for the existence of a negative slope I-V relation. Further, excitation does not appear to be a direct consequence of the Na(+) pump.

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