cardiac cycle when these ion channels are open.The movements of the ions produce currents that form the basis of the cardiac action potential.Individual channels are relatively ion-specific,and the flux of ions through them is thought to be controlled by "gates"(probably flexible peptide chains or energy barriers).Each type of channel has its own type of gate(sodium,calcium,and some potassium channels are each thought to have two types of gates),and each type of gate is opened and closed by specific transmembrane voltage,ionic,or metabolic conditions. At rest,most cells are not significantly permeable to sodium,but at the start of each action potential,they become quite permeable (see below).In electrophysiologic terms,the conductance of the fast sodium channel suddenly increases in response to a depolarizing stimulus.Similarly,calcium enters and potassium leaves the cell with each action potential.Therefore,in addition to ion channels,the cell must have mechanisms to maintain stable transmembrane ionic conditions by establishing and maintaining ion gradients.The most important of these active mechanisms is the sodium pump,Na/K ATPase.This pump and other active ion carriers contribute indirectly to the transmembrane potential by maintaining the gradients necessary for diffusion through channels.In addition,some pumps and exchangers produce net current flow(eg,by exchanging three Na"for two K*ions)and hence are termed "electrogenic." When the cardiac cell membrane becomes permeable to a specific ion (ie when the channels selective for that ion are open),movement of that ion across the cell membrane is determined by Ohm's law:current voltage resistance,or current voltage conductance.Conductance is determined by the properties of the individual ion channel protein.The voltage term is the difference between the actual membrane potential and the reversal potential for that ion(the membrane potential at which no current would flow even if channels were open).For example,in the case of sodium in a cardiac cell at rest,there is a substantial concentration gradient (140 mmol/L Na"outside;10-15 mmol/L Na"inside)and an electrical gradient (0 mV outside:-90 mV inside)that would drive Na'into cells.Sodium does not enter the cell at rest because sodium channels are closed;when sodium channels open,the very large influx of Na'ions accounts for phase 0 depolarization.The situation for K*ions in the resting cardiac cell is quite different.Here,the concentration gradient (140 mmol/L inside;4 mmol/L outside)would drive the ion out of the cell,but the electrical gradient would drive it in;that is,the inward gradient is in equilibrium with the outward gradient.In fact,certain potassium channels("inward rectifier"channels) are open in the resting cell,but little current flows through them because of this balance.The equilibrium,or reversal potential,for ions is determined by the Nernst equation: where Ce and Ci are the extracellular and intracellular concentrations,respectively, multiplied by their activity coefficients.Note that raising extracellular potassium makes Ek less negative.When this occurs,the membrane depolarizes until the new Ek 44 cardiac cycle when these ion channels are open. The movements of the ions produce currents that form the basis of the cardiac action potential. Individual channels are relatively ion-specific, and the flux of ions through them is thought to be controlled by "gates" (probably flexible peptide chains or energy barriers). Each type of channel has its own type of gate (sodium, calcium, and some potassium channels are each thought to have two types of gates), and each type of gate is opened and closed by specific transmembrane voltage, ionic, or metabolic conditions. At rest, most cells are not significantly permeable to sodium, but at the start of each action potential, they become quite permeable (see below). In electrophysiologic terms, the conductance of the fast sodium channel suddenly increases in response to a depolarizing stimulus. Similarly, calcium enters and potassium leaves the cell with each action potential. Therefore, in addition to ion channels, the cell must have mechanisms to maintain stable transmembrane ionic conditions by establishing and maintaining ion gradients. The most important of these active mechanisms is the sodium pump, Na+ /K+ ATPase. This pump and other active ion carriers contribute indirectly to the transmembrane potential by maintaining the gradients necessary for diffusion through channels. In addition, some pumps and exchangers produce net current flow (eg, by exchanging three Na+ for two K+ ions) and hence are termed "electrogenic." When the cardiac cell membrane becomes permeable to a specific ion (ie when the channels selective for that ion are open), movement of that ion across the cell membrane is determined by Ohm's law: current = voltage resistance, or current = voltage conductance. Conductance is determined by the properties of the individual ion channel protein. The voltage term is the difference between the actual membrane potential and the reversal potential for that ion (the membrane potential at which no current would flow even if channels were open). For example, in the case of sodium in a cardiac cell at rest, there is a substantial concentration gradient (140 mmol/L Na+ outside; 10-15 mmol/L Na+ inside) and an electrical gradient (0 mV outside; -90 mV inside) that would drive Na+ into cells. Sodium does not enter the cell at rest because sodium channels are closed; when sodium channels open, the very large influx of Na+ ions accounts for phase 0 depolarization. The situation for K+ ions in the resting cardiac cell is quite different. Here, the concentration gradient (140 mmol/L inside; 4 mmol/L outside) would drive the ion out of the cell, but the electrical gradient would drive it in; that is, the inward gradient is in equilibrium with the outward gradient. In fact, certain potassium channels ("inward rectifier" channels) are open in the resting cell, but little current flows through them because of this balance. The equilibrium, or reversal potential, for ions is determined by the Nernst equation: where Ce and Ci are the extracellular and intracellular concentrations, respectively, multiplied by their activity coefficients. Note that raising extracellular potassium makes EK less negative. When this occurs, the membrane depolarizes until the new EK