Adaptive response by state-dependent inactivation

Abstract

Many membrane channels and receptors exhibit adaptive, or desensitized, response to a strong sustained input stimulus. A key mechanism that underlies this response is the slow, activitydependent removal of responding molecules to a pool which is unavailable to respond immediately to the input. This mechanism is implemented in different ways in various biological systems and has traditionally been studied separately for each. Here we highlight the common aspects of this principle, shared by many biological systems, and suggest a unifying theoretical framework. We study theoretically a class of models which describes the general mechanism and allows us to distinguish its universal from systemspecific features. We show that under general conditions, regardless of the details of kinetics, molecule availability encodes an averaging over past activity and feeds back multiplicatively on the system output. The kinetics of recovery from unavailability determines the effective memory kernel inside the feedback branch, giving rise to a variety of system-specific forms of adaptive response-precise or input-dependent, exponential or power-law-as special cases of the same model. adaptation | feedback | signal-processing | biochemical networks M any sensing molecules, such as membrane channels and receptors, have mechanisms of activity attenuation following exposure to strong, persistent stimulation. Sometimes termed "adaptation" or "desensitization," the quantitative hallmark of these responses is that an abrupt change in stimulus elicits a strong rapid rise in activity followed by a slower relaxation to steady state. Such responses have been studied extensively in the context of sensory systems (1) as well as cellular signaling systems (2, 3). They are thought to reflect the continuous need of a sensory system to adjust to changing external conditions while coping with limited resources and suggest connections to such concepts as homeostasis (4) and feedback control (5).A widely encountered mechanism underlying adaptive response is the slow activity-dependent modulation in the total number of molecules available to respond. This is a well-known phenomenon that characterizes a large class of biological systems and can be implemented physically in many ways; Fig. 1 illustrates voltage-gated ion channels (6, 7), bacterial chemotactic (8, 9) and G protein-coupled receptors (10) as typical examples. These receptors and channels can all become temporarily unavailable to respond to the external signal via either a change of protein conformation that blocks the channel pore (ion channels), covalent modifications (chemotactic receptors), or their physical removal from the cell surface (internalization of GPCR or trafficking in some synaptic receptors)(11). In all these examples transitions to the unavailable state are strongly dependent on the activity state of the molecule (e.g., primarily through open channels or through ligand-bound receptors). Despite these apparent common principles, differences in morphology and context have tr...

Linking the Computational Structure of Variance Adaptation to Biophysical Mechanisms

“…The adaptive properties of kinetic models that represent biochemical processes including neurotransmitter receptors have recently been analyzed from a theoretical point of view (Friedlander and Brenner, 2009). This previous work showed that first order kinetic systems similar to the type discussed here can change their gain when receptors become unavailable.…”

Common dynamical features of sensory adaptation in photoreceptors and olfactory sensory neurons

“…The ability of a biological system to adjust the sensitivity in a wide range of input amplitudes, has been extensively studied in the literature10111213, especially in recent years1415161718192021222324. The phenomenon occurs in different contexts, like chemotaxis in bacteria1424 and amoeba19, osmotic regulation in yeast25, tryptophan regulation in E.coli 26, and sensory systems171213.…”

Stable swarming using adaptive long-range interactions

“…The response usually includes a strong transient part, followed by adaptation which determines the steady-state at longer-times. Famous examples include cell receptors [5] and molecular signaling tasks in cells [6][7][8][9], as well as collective behaviour which is based on chemical signaling [10] such as in the case of bacteria [11]. Another important example on the cellular level is chemotaxis [12][13][14].…”