Photochromic Potassium Channel Blockers: Design and Electrophysiological Characterization

Voltage-gated potassium (K _v ) channels are membrane proteins that open a selective pore upon membrane depolarization, allowing K⁺ ions to flow down their electrochemical gradient. In neurons, K _v channels play a key role in repolarizing the membrane potential during the falling phase of the action potential, often resulting in an after hyperpolarization. Opening of K _v channels results in a decrease of cellular excitability, whereas closing (or pharmacological block) has the opposite effect, increased excitability. We have developed a series of photosensitive blockers for K _v channels that enable reversible, optical regulation of potassium ion flow. Such molecules can be used for remote control of neuronal excitability using light as an on/off switch. Here we describe the design and electrophysiological characterization of photochromic blockers of ion channels. Our focus is on K _v channels but in principle, the techniques described here can be applied to other ion channels and signaling proteins.