A biological function is supposed to be performed adequately, and hence may fail to do so: this is dysfunction. This raises two questions. One is how to make explicit the way in which function can be discriminated from dysfunction without confusing dysfunction with non-function. The second question is how what is “right” and “wrong” can be legitimated by natural regulatory norms. A function can be viewed as a quality to which at least one variable with a definite set of values (...) is associated. Accordingly, function and dysfunction are the same quality of the same trait, but differ in the values associated to this variable. Dysfunction occurs when the associated set of values does not match this normal state. Biological systems have the epistemic singularity that their existence is the consequence of two distinct causal regimes, the so-called “proximate” and “ultimate” causes, whose convergence defines a system’s prescriptive normality. Each cause imposes restrictive rules that limit the possible ways these systems can putatively exist. When a system is insensitive to ultimate cause, it is determined by proximate causation alone, and hence escapes its own prescriptive norms. In conclusion: The normality of a biological system is defined by the convergence of proximate and ultimate causes. A function is a variable-associated quality whose values are defined relative to the norms of the system. Dysfunction occurs when the set of values of the same variable does not match the normality of the system, which can occur when the system is insensitive to ultimate causation. (shrink)

Stimulation of airway myocytes by contractile agents such as acetylcholine (ACh) activates a Ca2+-activated Cl– current (IClCa) which may play a key role in calcium homeostasis of airway myocytes and hence in airway reactivity. The aim of the present study was to model IClCa in airway smooth muscle cells using a computerised model previously designed for simulation of cardiac myocyte functioning. Modelling was based on a simple resistor-battery permeation model combined with multiple binding site activation by calcium. In order to (...) validate the model, a combination of equations, used to mimic [Ca2+]i response to ACh stimulation, were incorporated into the model. The results indicate that the model developed in this article accounts for experimental recordings and electrophysiological characteristics of this current in airway smooth muscle cells, with parameter values consistent with those calculated from experimental data. Such a model may thus be used to predict IClCa functioning, though additional experimental data from airway myocytes would be useful to more accurately determine some parameter values of the model. (shrink)