Membrane potential depends on the concentration gradient of ions across the membrane and on the membrane permeability for these ions. The resting membrane potential of most cells has a negative value in respect to cell exterior. Any stimulus that triggers the flow of ions across the membrane results in a change of membrane potential. Cells respond to a stimulus with graded potential or a generation of action potentials. The latter is a rapid transient depolarization of membrane potential due to a change in membrane permeability for ions characteristic of excitable cells. The generation of the action potential can only be initiated with a threshold stimulus that depolarizes the membrane to the threshold value. This increases the opening probability of voltage-gated Na+ channels and Na+ ions influx into the cell. The result is a rapid membrane depolarization which is followed by the opening of voltage-gated K+ channels that, in conjunction with voltage-gated Na+ current inactivation, repolarizes the membrane. The shape and the amplitude of the action potential are determined by the activation and inactivation properties of voltage-gated ion channels and not by the intensity of the stimulus. The normal function of voltage-gated ion channels is of utmost importance for normal cell excitability and mutations in ion channels can lead to their dysfunction and thereby to the malfunction of excitable tissues like muscles, heart, or brain.