Voltage-gated potassium (K v) channels are members of a large super-family of cation channels that include sodium and calcium channels. They form ion selective pores that span across the plasma membrane. Opening and closing (termed as gating) of the pores is controlled by membrane potential that exists across the cell membrane: they open when the membrane is depolarized and close when hyperpolarized. A number of vital activities of the body, including nerve conduction, beating of the heart and secretion of hormones, are dependent on the voltage gating property of these channels. Consequently, inherited mutations in the genes encoding these channels lead to diseases of the nervous system (e.g. epilepsy), heart (e.g. arrhythmia) and endocrine organs. Although a large number of drugs targeted to known ion channels are already in clinical use, the discovery of novel members of this super-family by the genome sequencing projects opened up fresh opportunities for development of new drugs. For a full realization of their potential, however, it is important to understand the mechanism by which they work at the molecular level. Despite significant research, our understanding of how they sense changes in membrane voltage and transmit the signal to channel gates remains highly controversial.

Kv channels are made up of four subunits each comprising six membrane embedded segments, termed S1-S6; S1-S4 form the voltage sensing module (the charged S4 being the key component) and S5-S6 the pore domain . The former is responsible for voltage sensing and the latter for selective ion permeation. The two functions are coupled in such as way that when the membrane voltage is depolarized the voltage sensor undergoes conformational changes that triggers movement of gates from closed to open state. As a result, K+ ions move through the open pore.

The main aim is to know that:

1.What are the conformational changes that the voltage-sensing domain undergoes during gating?

2.How do these conformational changes trigger the opening of pore gates?

3.I am also interested to study the interaction of the potassium channel with the natural or synthetic toxins as we know that they represent the important class of drug target.

I am further very much interested to look into the molecular mechanism of these channel in detail and reveal the mystery behind this. I would like to combine bioinformatics tools with experimental work to get information about the details of the interactions involved in gating which is not possible to get in experimental analysis. I am confident that the knowledge and experience I have recently gained in this particular field will help me.