Ions move across the cell membrane through specific ion channels. When these channels open, the permeability and electrical conductance to their respective ions increases, which leads to a change in the membrane potential.
The membrane potential in a resting cell is near the equilibrium potential for K+. That occurs because the membrane is relatively more permeable in the resting state to K+ than to other ions such as Na+ and Ca++. Therefore, the membrane potential reflects not only the concentration gradients of individual ions (i.e., the equilibrium potentials), but also the relative permeability of the membrane to those ions. If the membrane has a very high permeability to one ion over all the others, then that ion will have a greater influence on determining the membrane potential. One way to express this relationship is by the Goldman-Hodgkin-Katz equation, which can be expressed is as follows:
Em = g'K (EK) + g'Na (ENa) + g'Ca (ECa) + g'Cl (ECl)
The membrane potential (Em) depends on the sum of the individual equilibrium potentials multiplied by the relative membrane conductance for the ionic species. The relative conductance (g’X) of a specific ion is the conductance for that ion divided by the total conductance for all the ionic species (i.e., g’X = gX/gTotal).
If the equilibrium potential values for a typical myocyte are incorporated into the above equation describing Em, then
Em = g'K (-96 mV) + g'Na (+52 mV) + g'Ca (+134 mV) + g'Cl (-90 mV)
In a cardiac cell, the individual ion concentration gradients change very little, even when Na+ and Ca++ enter the cell, and K+ leaves the cell during action potentials. Therefore, changes in Em are primarily because of changes in ion conductances and the associated changes in ion currents. For example, in a resting cell, g'K is very high relative to all the other ion conductances, so the Em (about -90 mV) is near the EK in a resting, repolarized cell. At the peak of an action potential, g'Na is very high relative to the other ions, therefore the Em (about +20 mV in cardiomyocytes) approaches ENa. In the heart, the most important ions determining the membrane potential are Na+, K+ and Ca++.
Ion conductances are altered by antiarrhythmic drugs that block specific ion channels. Sodium-channel blockers such as quinidine inactivate fast-sodium channels and reduce the conductance of sodium ions into the cell. Calcium-channel blockers such as verapamil and diltiazem decrease calcium conductance into the cell. Potassium-channel blockers decrease potassium conductance.