scholarly journals The Modulated Receptor Hypothesis Revisited from the Viewpoint of Myocardial Interstitial Potential.

1994 ◽  
Vol 13 (5) ◽  
pp. 263-274
Author(s):  
Toru MARUYAMA ◽  
Yoshikazu KAJI ◽  
Yoshiyuki NIHO
Keyword(s):  
Modulated Receptor ◽  
Interstitial Potential

Use of ionic currents to identify and estimate parameters in models of channel blockade

1990 ◽  
Vol 259 (2) ◽  
pp. H626-H634
Author(s):  
C. F. Starmer ◽  
V. V. Nesterenko ◽  
F. R. Gilliam ◽  
A. O. Grant
Keyword(s):  
Time Course ◽  
Experimental Studies ◽  
Ionic Currents ◽  
Blocking Agent ◽  
Model Parameters ◽  
Protein Conformations ◽  
Channel Blockade ◽  
Channel Blocking ◽  
Individual Contributions ◽  
Modulated Receptor

Models of ion channel blockade are frequently validated with observations of ionic currents resulting from electrical or chemical stimulation. Model parameters for some models (modulated receptor hypothesis) cannot be uniquely determined from ionic currents. The time course of ionic currents reflects the activation (fraction of available channels that conduct in the presence of excitation) and availability of channels (the ability of the protein to make a transition to a conducting conformation and where this conformation is not complexed with a drug). In the presence of a channel blocking agent, the voltage dependence of availability appears modified and has been interpreted as evidence that drug-complexed channels exhibit modified transition rates between channel protein conformations. Because blockade and availability both modify ionic currents, their individual contributions to macroscopic conductance cannot be resolved from ionic currents except when constant affinity binding to a bindable site is assumed. Experimental studies of nimodipine block of calcium channels and lidocaine block of sodium channels illustrate these concepts.

Cardiac microimpedance measurement in two-dimensional models using multisite interstitial stimulation

2006 ◽  
Vol 290 (5) ◽  
pp. H1976-H1987 ◽  
Author(s):  
Andrew E. Pollard ◽  
Roger C. Barr
Keyword(s):  
Test Data ◽  
Ventricular Myocytes ◽  
Electrophysiological Study ◽  
Two Dimensional ◽  
Dynamic Membrane ◽  
Anisotropic Models ◽  
Wide Range ◽  
Dimensional Models ◽  
Generate Test Data ◽  
Interstitial Potential

We analyzed central interstitial potential differences during multisite stimulation to assess the feasibility of using those recordings to measure cardiac microimpedances in multidimensional preparations. Because interstitial current injected and removed using electrodes with different proximities allows modulation of the portion of current crossing the membrane, we hypothesized that multisite interstitial stimulation would give rise to central interstitial potential differences that depend on intracellular and interstitial microimpedances, allowing measurement of those microimpedances. Simulations of multisite stimulation with fine and wide spacing in two-dimensional models that included dynamic membrane equations for guinea pig ventricular myocytes were performed to generate test data (∂φo). Isotropic interstitial and intracellular microimpedances were prescribed for one set of simulations, and anisotropic microimpedances with unequal ratios (intracellular to interstitial) along and across fibers were prescribed for another set of simulations. Microimpedance measurements were then obtained by making statistical comparisons between ∂φo values and interstitial potential differences from passive bidomain simulations (Δφo) in which a wide range of possible microimpedances were considered. Possible microimpedances were selected at 25% increments. After demonstrating the effectiveness of the overall method with microimpedance measurements using one-dimensional test data, we showed microimpedance measurements within 25% of prescribed values in isotropic and anisotropic models. Our findings suggest that development of microfabricated devices to implement the procedure would facilitate routine measurement as a component of cardiac electrophysiological study.

The effect of calcium and Ca antagonists upon excitation–contraction coupling

1987 ◽  
Vol 65 (4) ◽  
pp. 717-723 ◽  
Author(s):  
H. C. Lüttgau ◽  
G. Gottschalk ◽  
Dorothea Berwe
Keyword(s):  
Sulfate Solution ◽  
Muscle Fibres ◽  
Force Development ◽  
Controlling System ◽  
Ca Antagonist ◽  
State Potential ◽  
Skeletal Muscle Fibres ◽  
Modulated Receptor ◽  
Transient Force ◽  
Steady State Potential

The effect of a Ca2+ -free tetraethylammonium sulfate solution on force development in short skeletal muscle fibres of the frog was investigated under voltage clamp control. Maximum force could still be reached under this condition. The removal of external Ca2+, however, caused an acceleration of force inactivation leading to a shift of the steady-state potential dependence of force inactivation to more negative potentials. With reference to the "modulated-receptor hypothesis" this result was explained by assuming a potential-dependent binding of Ca2+ to a force-controlling system in the T-tubular membrane, with a low affinity in the depolarized-inactivated state. A dissociation of Ca2+ is assumed to turn the system into a secondary inactivated state (paralysis) from which it only slowly recovers after repolarization. Ca antagonists like D600 and diltiazem accelerated the shift into paralysis, probably by an allosteric displacement of Ca2+ from its binding site. The application of 1–2 μM of the Ca antagonist nifedipine blocked the inward Ca2+ current and caused a prolongation of the transient force development following a depolarization. A similar retardation of force inactivation and a threshold shift to more negative potentials occurred when the Ca2+ chelator ethyleneglycol-bis (β-aminoethyl ether)-N,N′-tetraacetic acid (EGTA) was injected into the fibre and when in Ca2+-free solutions sodium ions entered the cell through Ca2+ channels.

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