Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism. This means no trigger is required for their opening and closing, hence the reference to leaking. There is no actual event that opens the channel; instead, it has an intrinsic rate of switching between the open and closed states. These channels are found throughout the neuron and contribute to the resting transmembrane voltage of the excitable membrane. For example, the potassium and sodium leak channels along with the sodium-potassium pump help maintain the neuron's resting membrane potential. The movement of the potassium ions down the electrochemical gradient via leakage channels creates a negative polarity inside the cell. This allows sodium ions to enter slowly through the sodium leak channels to prevent the neuron's membrane potential from constantly dropping lower than -70mV. At this level, the sodium-potassium pump will balance the concentration of sodium and potassium ions across the membrane.
Potassium leak channels like the two-pore domain potassium (K2P) family are widely distributed in the peripheral and central nervous systems, where they are targets for novel analgesic agents. When the activity of potassium leak channels decreases during inflammatory and neuropathic pain conditions, pain sensation is enhanced. Thus, drugs help activate these potassium leak channels to mitigate the pain.
