inactivation of the Na+ channels by the inner gate (inactivation gate), reducing the movement of sodium into the cell. At the same time potassium channels (called Ito1) open and close rapidly, allowing for a brief flow of potassium ions out of the cell, making the membrane potential slightly more negative. This is referred to as a 'notch' on the action potential waveform. There is no obvious phase 1 present in pacemaker cells. Phase 2 This phase is also known as the "plateau" phase due to the membrane potential remaining almost constant, as the membrane slowly begins to repolarize. This is due to the near balance of charge moving into and out of the cell. During this phase delayed rectifier potassium channels (Iks) allow potassium to leave the cell while L-type calcium channels (activated by the influx of sodium during phase 0) allow the movement of calcium ions into the cell. These calcium ions bind to and open more calcium channels (called ryanodine receptors) located on the sarcoplasmic reticulum within the cell, allowing the flow of calcium out of the SR. These calcium ions are responsible for the contraction of the heart. Calcium also activates chloride channels called Ito2, which allow Cl− to enter the cell. Increased calcium concentration in the cell also increases activity of the sodium-calcium exchangers, while increased sodium concentration (from the depolarisation of phase 0) increases activity of the sodium-potassium pumps. The movement of all these ions results in the membrane potential remaining relatively constant, with K+ outflux, Cl− influx as well as Na+/K+ pumps contributing to repolarisation and Ca2+ influx as well as Na+/Ca2+ exchangers contributing to depolarisation. This phase is responsible for the large duration of the action potential and is important in preventing irregular heartbeat (cardiac arrhythmia). There is no plateau phase present in pacemaker action potentials. Phase 3 During phase 3 (the "rapid repolarization" phase) of the action potential, the L-type Ca2+ channels close, while the slow delayed rectifier (IKs) K+ channels remain open as more potassium leak channels open. This ensures a net outward positive current, corresponding to negative change in membrane potential, thus allowing more types of K+ channels to open. These are primarily the rapid delayed rectifier K+ channels (IKr) and the inwardly rectifying K+ current, IK1. This net outward, positive current (equal to loss of positive charge from the cell) causes the cell to repolarize. The delayed rectifier K+