Electrophysiology modeling

Coupled biochemical systems and membrane transport 7.3 Electrophysiology modeling 

---

Figure 5 The C y-normalized cross-species exposure-response continuum for 7 across multiple pharmacology models [42]. A listed value (Cx) is the C iU (nM) affecting a response in assay X. RAM(r), rat radial arm maze DSR(nhp), nonhuman primate delayed spatial response task e-phys(r), rat electrophysiology model NOR(r), rat novel object recognition cGMP(m,r), mouse/rat cerebellar cGMP trem(nhp), nonhuman primate tremor rot(m), mouse rotarod.

In electrophysiology modeling biological membranes are typically treated as capacitors with constant capacitance. The basic equation for a capacitor is ... 

Here we present a computational model of mitochondrial electrophysiology and oxidative phosphorylation is based on the models of one of the authors [13, 14] and Wu et al. [212], The processes illustrated in Figure 7.9 are modeled based on the electrophysiology modeling approach outlined in Section 7.3. Thermodynamic constants for the transport reactions are computed from thermodynamic data tabulated in Table 6.1. 

Angersbach, A., Heinz, V, Knorr, D., 1999. Electrophysiological model of intact and processed plant tissues Cell disintegration criteria. Biotechnol. Prog. 15 753-762. 

These detailed cell models can be used to study the development in time of processes like myocardial ischaemia (a reduction in coronary blood flow that causes under-supply of oxygen to the cardiac muscle), or effects of genetic mutations on cellular electrophysiology. They allow to predict the outcome of changes in the cell s environment, and may even be used to assess drug actions. 

The individual modules of the in situ heart can be coupled together to compute a whole sequence from ventricular pressure development, coronary perfusion, tissue supply of metabolites, cell energy consumption, and electrophysiology, to contractile activity and ventricular pressure development in the subsequent beat. The starting point (here chosen as ventricular pressure development) can be freely selected, and drug effects on the system can be simulated. Inserted into a virtual torso, these models allow one to compute the spread of excitation, its cellular basis, and the consequences for an ECG under normal and pathological conditions. 

Just a year after Stephenson s classical paper of 1956, J. del Castillo and B. Katz published an electrophysiological study of the interactions that occurred when pairs of agonists with related structures were applied simultaneously to the nicotinic receptors at the endplate region of skeletal muscle. Their findings could be best explained in terms of a model for receptor activation that has already been briefly introduced in Section 1.2.3 (see particularly Eq. (1.7)). In this scheme, the occupied receptor can isomerize between an active and an inactive state. This is very different from the classical model of Hill, Clark, and Gaddum in which no clear distinction was made between the occupation and activation of a receptor by an agonist. 

Not applicable — the common fruit fly has been an important model in medicine and population genetics for much of the last century. It is suitable for many types of studies, including electrophysiology... 

Lenoir, Timothy. 1986. Models and Instruments in the Development of Electrophysiology, 1845-1912. Historical Studies in the Physical and Biological Sciences 17 1 (1986) 1-54. 

These findings were confirmed and extended by in vitro electrophysiological studies of slices from normal animals that revealed that subtle (e.g. 20%) reductions of inhibitory synaptic function could lead to epileptiform activity. Importantly, activation of excitatory synapses is often pivotal in the expression of a seizure in distinct models in vitro. In addition to these important pharmacological observations, electrophysiological analyses of individual neurons during a partial seizure revealed that neurons undergo a massive depolarization and fire action potentials at high frequencies (Fig. 37-1) [3], This pattern of... 

Recurrences of mood episodes causes behavioral sensitivity and electrophysiologic kindling (similar to the amygdala-kindling models for seizures in animals) and can result in rapid or continuous mood cycling. 

---