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G W Beeler

Publications and source records attributed to G W Beeler.

29 records · Page 2Linked to original sources

Voltage clamp experiments on ventricular myocarial fibres.

1. A voltage clamp method utilizing a sucrose gap and glass microelectrodes was developed and used to study dog ventricular myocardial fibre bundles. The limitations and the reliability of this method are demonstrated by a series of tests.2. A dynamic sodium current, excited at membrane potentials more positive than -65 mV, was measured. The equilibrium potential for this large, rapid inward current depends directly on [Na](o), shifting 29.0 +/- 2.3 mV (+/- S.E. of mean), as opposed to a theoretically expected value of 30.6 mV, when [Na](o) is reduced to 31% of normal.3. Sodium current is inactivated by conditioning depolarizations. Complete inactivation occurs with conditioning potentials more positive than -45 mV, and 50% inactivation occurs at about -55 mV. The location of the inactivation curve shifts along the voltage axis, when [Ca](o) is varied between 0.2 and 7.2 mM.4. A second, much smaller and slower net inward current, with a threshold around -30 mV, and an equilibrium potential above +40 mV was also observed.5. The ;steady-state' current-voltage relationship (after 300-600 msec) exhibits inward-going (anomalous) rectification with negative slope between -50 and -25 mV.6. A small, very slowly developing component of outward current was observed at inside positive potentials. The equilibrium potential for this current, although slightly dependent on [K](o), is neither identical with the potassium equilibrium potential nor with the resting potential in normal Tyrode solution.7. Anatomical limitations, primarily resistance in the extracellular space within the bundle, prevent complete characterization of the rapid, large sodium current, but do not limit the application of the clamp method to the study of other, smaller and slower currents. The evidence for this is discussed extensively in the Appendix.

Animals↗

Membrane calcium current in ventricular myocardial fibres.

1. A slow inward current in ventricular preparations of the dog heart can be measured by the voltage clamp method without interference from the initial rapid sodium current if the sodium system is inactivated by conditioning depolarization.2. The slow inward current is very sensitive to variation in [Ca](o). It occurs above the equilibrium potential of I(Na) immediately after changing the bathing fluid to a sodium-free solution and persists under this condition for a long time without much alteration, while I(Na) is rapidly abolished. Tetrodotoxin and [Mg](o) have no effect on this current component. These results strongly support the view that the slow inward current in cardiac tissue is carried by calcium ions.3. The threshold for initiation of the calcium current is around -35 mV in Tyrode solution and is shifted to more negative potentials by either increasing [Ca](o) or reducing [Na](o).4. Calcium sensitive inward current tails associated with repolarization are assumed to represent a proportional measure of calcium conductance activated during the preceding depolarization. Calcium conductance declines rapidly with time in the inside negative potential range and slowly at positive potentials. The time constants for this ;inactivation' process vary between 40 and 700 msec in the potential range -35 to +50 mV.5. By using instantaneous current-voltage relations the reversal potential of calcium current was estimated to be about +60 mV in normal Tyrode solution. As shown in the Appendix, however, the calcium equilibrium potential cannot be considered to be constant.6. The importance of the calcium current for the plateau of the cardiac action potential is discussed.

Animals↗

The relation between membrane potential, membrane currents and activation of contraction in ventricular myocardial fibres.

1. Membrane currents and contractile responses have been measured in ventricular myocardial preparations under voltage clamp conditions.2. In Tyrode solution, steady-state contraction was obtained only after 5-8 depolarizations to a given potential level. The threshold of steady-state tension was identical to the potential where the calcium inward current, I(Ca), was activated (about -35 mV). Both thresholds were shifted in the same direction along the voltage axis and by the same amount by changing [Ca](o) or [Na](o). Maximum tension was obtained at inside positive potentials.3. The time courses of steady-state tension and of activation of I(Ca) were different by more than one order of magnitude in Tyrode solution. But in order to achieve any appreciable steady-state tension, I(Ca) had to flow during several identical depolarizations. Tension decreased again at potentials above E(Ca). This suggests that calcium inward current must flow in order to fill intracellular calcium stores from which calcium can be released by an unknown mechanism.4. The ability of a fibre bundle to contract again after a preceding twitch is greatly dependent on the membrane potential between two equal depolarizations. In Tyrode solutions with 1.8 and 7.2 mM-CaCl(2) half restoration of this ability occurred at -45 +/- 3 mV (+/- S.E. of mean) and -23 +/- 4 mV, respectively.5. In sodium-free bathing solutions, steady-state tension was attained upon the first depolarization provided I(Ca) was activated. Furthermore, at different potentials, the time courses of activation of tension and of activation of I(Ca) were identical, i.e. tension reached its maximum when I(Ca) was fully activated. This suggests that in sodium-free solutions the flow of calcium ions into the fibre directly activates contraction.

Animals↗

Sodium current in ventricular myocardial fibers.

Membrane currents were measured in thin bundles of dog ventricular myocardium under voltage-clamp conditions. A rather large initial inward current which had an equilibrium potential at about + 55 millivolts could be recorded. When the external sodium concentration was reduced, the equilibrium potential for this current was shifted by the amount predicted theoretically for a current carried solely by sodium ions. The size of the sodium inward current (I(Na)) was largely dependent on the preceding membrane potential. The I(Na) was completely inactivated if the membrane potential was as low as -45 millivolts. Sodium ions are the main carrier of charge during the rapid depolarization phase of the action potential.

Action Potentials↗

Calcium current and activation of contraction in ventricular myocardial fibers.

In thin bundles of dog ventricular myocardium, a slow inward current (distinct from the sodium inward current) could be recorded under voltageclamp conditions. This inward current was influenced by changes in external calcium concentration, but it was not dependent on external sodium concentration. Therefore, this current which contributes an appreciable amount of charge transfer during the plateau of the action potential, is carried by calcium ions. In sodium-free solution, the flow of calcium ions into the fiber is directly related to activation of contraction. In sodium-containing solution, however, calcium inward current serves primarily to fill up some intracellular stores from which calcium can be released by moderate depolarization.

Action Potentials↗

Taking HL7 to the next level.

For HL7 to reach the next level of standards capability, the organization must continue their model-centric development process so systems using the standards can achieve interoperability--sematic as well functional. The HL7 Message Development Framemwork specifies thi process detail and anchors future HL7 standards with a common reference information model. That model will evolve through a process of discussion, amendment, voting to continuously harmonize proposals from committees that have specific spheres of knowledge.

Computer Communication Networks↗