L-type CACNA1/Cav 1.2 current T-type CACNA1G,H/Cav 3.1, 3.2 transient lto,f KCND3/Kv 4.3 outward lto,s KCNA4/Kv 1.4 lKur KCNA5/Kv 1.5 lK,ACh KCNJ3, 5/Kir 3.1, 3.4 lCl CFTR/CFTR inward rectifier, lK1 KCNJ2/Kir 2.1 pacemaker current, lf HCN2, 4/HCN2, 4 Na+/Ca2+ exchange SLC8A1/NCX 1
Na+/K+-ATPase NKAIN1-4/Na, K-pump
FIGURE 14–2 Schematic diagram of the ion permeability changes and transport processes that occur during an action potential and the diastolic period following it. Yellow indicates inward (depolarizing) membrane currents; blue indicates outward (repolarizing) membrane currents. Multiple subtypes of potassium and calcium currents, with different sensitivities to blocking drugs, have been identified. The right side of the figure lists the genes and proteins responsible for each type of channel or transporter.
equilibrium potential, EK (about –90 mV when Ke = 5 mmol/L and Ki = 150 mmol/L). It also explains why small changes in extracellular potassium concentration have significant effects on the resting membrane potential of these cells. For example, increasing extracellular potassium shifts the equilibrium potential in a positive direction, causing depolarization of the resting membrane potential. It is important to note, however, that potassium is unique in that changes in the extracellular concentration can also affect the permeability of potassium channels, which can produce some nonintuitive effects (see Box: Effects of Potassium).
The upstroke (phase 0) of the action potential is due to the inward sodium current (INa). From a functional point of view, the behavior of the channels responsible for this current can be described in terms of three states (Figure 14–3). It is now recognized that these states actually represent different conformations of the channel protein. Depolarization of the membrane by an impulse propagating from adjacent cells results in opening of the activation (m) gates of sodium channels (Figure 14–3, middle), and sodium permeability is markedly increased. Extracellular sodium is then able to diffuse down its electrochemical gradient into the cell, causing the membrane potential to move very rapidly toward the sodium equilibrium potential, ENa (about +70 mV when Nae = 140 mmol/L and Nai = 10 mmol/L). As a result, the maximum upstroke velocity of the action potential is very fast. This intense influx of sodium is very brief because opening of the m gates upon depolarization is promptly followed by closure of the h gates and inactivation of these channels (Figure 14–3, right). This inactivation contributes to the early repolarization phase of the action potential (phase 1). In some cardiac myocytes, phase 1 is also due to a brief increase in