Molecular physiology of voltage-gated ion channels

Voltage-gated ion channels are key players in all biological systems where they generate and modulate for instance the nervous impulse and pacemaker activity in the heart and the brain.

We study the voltage-sensing mechanism of several ion channels by expressing cloned channels in Xenopus oocytes and measuring ion and gating currents with several electrophysiological methods such as the two-electrode voltage clamp and patch-clamp techniques. Computer simulations are used to understand the molecular effects at the cellular level.

Specifically we are studying how different small-molecule compounds can affect ion channel activity. Instead of blocking the ion conducting pore to modify neuronal and cardiac activity we have proposed that medical drugs can target the voltage sensor. We have shown that negatively charged compounds like polyunsaturated fatty acids bind to the membrane close to the voltage sensor and thereby electrostatically affect the voltage-sensing mechanism. We have called this the lipoelectric mechanism. We are currently studying several families with lipoelectric properties. Hopefully, these compounds can be developed into medical drugs against cardiac arrhythmia, epilepsy and pain.

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