Ion Channel Blockade

Opening of ion-channels has been popularly described by means of Markov processes with a small number of important channel states. The approximation of the number of important states is often ambiguous and overestimating this number creates unnecessary computational complexities. We propose a simple equation that will portray the essence of voltage regulated ion-chan nel gating in a functional cell. The equation is generated using concepts in elementary thermodynamics applied to protein Markov models and it matches well many published channel current-voltage characteristics. Further, parameters of the model are found to be identifiable and easily determined from experimental data.

Electrical excitability and signaling, frequently associated with rapid responses to environmental stimuli, have been documented in both animals and higher plants. The presence of electrical potentials (EPs), such as action potentials (APs) and variation potentials (VPs), in plant cells suggests that plants make use of ion channels to transmit information over long distances. The reason why plants have developed pathways for electrical signal transmission is most probably the necessity to respond rapidly, for example, to environmental stress factors. We examined the nature and specific characteristics of the electrical response to wounding in the woody plant Persea americana (avocado). Under field conditions, wounds can be the result of insect activity, strong winds or handling injury during fruit harvest. Evidence for extracellular EP signaling in avocado trees after mechanical injury was expressed in the form of variation potentials. For tipping and pruning, signal velocities of 8.7 and 20.9 cm/s, respectively, were calculated, based on data measured with Ag/AgCl microelectrodes inserted at different positions of the trunk. EP signal intensity decreased with increasing distance between the tipping and pruning point and the electrode. Recovery time to pre-tipping or pre-pruning EP values was also affected by the distance and signal intensity from the tipping or pruning point to the specific electrode position. Real time detection of remote EP signaling can provide an efficient tool for the early detection of insect attacks, strong wind damage or handling injury during fruit harvest. Our results indicate that electrical signaling in avocado, resulting from microenvironment modifications, can be quantitatively related to the intensity and duration of the stimuli, as well as to the distance between the stimuli site and the location of EP detection. These results may be indicative of the existence of a specific kind of proto-nervous system in plants.

We describe a software library that we have developed to teach biophysics and physiology to undergraduate engineering and science students as well as to medical students. The library, which is under development, now includes software on: (1) the Hodgkin-Huxley model for excitation of action potentials in electrically excitable cells (such as nerve and muscle cells); (2) a random-walk model of

Research on ion channel modulation has become a hot topic because of the key roles these membrane proteins play in both prokaryotic and eukaryotic organisms. In this respect, lipid modulation adds to the overall modulatory mechanisms as a potential via to find new pharmacological targets for drug design based on interfering with lipid/channel interactions. However, our knowledge in this field is scarce and often circumscribed to the sites where lipids bind and/or its final functional consequences. To fully understand this process it is necessary to improve our knowledge on its molecular basis, from the binding sites to the signalling pathways that derive in structural and functional effects on the ion channel. In this review, we have compiled information about such mechanisms and established a classification into four different modes of action. Afterwards, we have revised in more detail the lipid modulation of Cys-loop receptors and of the potassium channel KcsA, which were chosen a...

Neurons communicate via a traveling wave of electrical excitation that propagates down an axon at speeds in the range of 10–100 m/s. This electrical wave is triggered and regulated by opening and closing of voltage-gated ion channels. These channels have been traditionally believed to be sensitive to the local electrochemical environment. A growing number of experiments now conclusively show that lipid-associated mechanical stimuli can control the channel response. We develop a quantitative model to elucidate the mechanosensitivity exhibited by these channels. With the help of a single model, we are able able to consolidate the fi ndings of the various experimental studies that have investigated the effect of different mechanical stimuli.

Ion channels are naturally occurring pores through the proteins that regulate the passage of ions and thus maintain the concentration of ions inside and outside the cell. The ion channels control many physiological functions and they can show selectivity for a specific ion. Ion channels are mostly observed in nerve cells and muscle cells. The influx of ions into cells can be regulated by a gate, like voltage controlled gate. Here we have investigated the ion transport through an ion channel by Poisson-Nernst-Plank model. In this model, proteins are approximated as cylindrical tubes embedded in a lipid membrane. Different ion channels with different channel radii are taken into consideration. The electrostatic potential, ion concentrations, ion flux and ion current are found. Simulation of ion channel is of vital importance in preparing biosensor where the molecular switching mechanism of ion-channel can regulate the flow of a particular ion in an analyte, if detected. The ion channe...