Potassium channels cardiac tissue

The potassium sparing diuretic, amiloride (43), also produces a Class III effect in cardiac tissue. In canine Purkinje fibres APD is increased by 35% after prolonged exposure to 5 /zM of the drug [121]. The authors suggest two potential mechanisms for this effect (1) delay of inactivation of Na+ channels, or (2) inhibition of Na+/Ca + exchange. In infarcted dogs which were subjected to a PES protocol to produce re-entrant ventricular arrhyth-... 

The excitable membrane of nerve axons, like the membrane of cardiac muscle (see Chapter 14) and neuronal cell bodies (see Chapter 21), maintains a resting transmembrane potential of -90 to -60 mV. During excitation, the sodium channels open, and a fast inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about -95 mV) repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues. 

Kv7.x channels encompass a gene family consisting of 5 distinct members denoted Kv7.1-Kv7.5. Kv7.1, also known as KvLQTl, is expressed primarily in non-neuronal tissues, including cardiac tissue where it contributes to repolarization of the cardiac action potential. Kv7.1 loss-of-function mutations are associated with long QT syndrome that can lead to a rare ventricular arrhythmia, torsades de pointes (Wang et al. 1996). The other members of the Kv7 family encode related potassium channels that are widely expressed... 

Bepridil. an atypical calcium channel antagonist, has antiarrhythmic activity, in addition to actions on the calcium channel. In addition to blockade of calcium channels, blockade of both sodium and potassium channels is manifested, which results in unique actions on cardiac tissue. 

Adenosine is a potent vasodilator that is produced endogenously. It mediates an outward flow of potassium from adenosine-sensitive potassium channels, stabilizing cardiac membranes. This results in a decrease in the duration of the atrial action potential, as well as negative chronotropic and inotropic actions. In addition, by stabilizing excitable tissue in the AV node, the drug effectively inhibits the conversion of paroxysmal atrial tachycardia to ventricular tachycardia, which could lead to fibrillation. 

Coelenterate toxins found in jellyfish and sea anemones bind to both sodium and potassium channels (Messerli, 2006). Coelenterates represent the earliest extant creature with a neuromuscular system. Toxins from the sea anemone are the best characterized cnidarian toxins in terms of mechanism of action, and more than 50 different toxins that target sodium VGICs have thus far been isolated or cloned (Honma, 2006). Each of these toxins can serve as a probe of sodium VGIC structure and function, and provide selectivity for sodium-dependent mechanisms in cardiac and neuronal tissues, to include autonomic nerves that mediate gastrointestinal symptoms in a variety of disease states. 

A. Type i drugs in general act by inhibiting the fast sodium channel responsible for Initial cardiac cell depolarization and Impulse conduction. Type la and type Ic drugs (which also block potassium channels) slow depolarization and conduction In normal cardiac tissue, and even at normal therapeutic doses the QT (types la and Ic) and QRS intervals (type Ic) are prolonged. Type lb drugs slow depolarization primarily in ischemic tissue and have little effect on normal tissue or on the ECG. In overdose, all type I drugs have the potential to markedly depress myocardial automaticity, conduction, and contractility. 

Purkinje cells is demonstrated in Figure 12.1 and, like all cardiac myocytes, can be divided into four phases. Phase 4 (pacemaker potential) involves the slow influx of sodium ions, depolarizing the cell until the threshold potential is reached. Once the threshold potential is reached, the fast sodium current is activated, resulting in a rapid influx of sodium ions causing cell depolarization (phase 0 rapid depolarization). Phase 1 (partial repolarization) involves the inactivation of sodium channels and a transient outward current. Phase 2 (plateau phase) results from the slow influx of calcium ions. Repolarization (phase 3) occurs as a result of outflow of potassium ions from the cell and restores the resting potential. There are variations between the different areas of the heart, specifically the nodal tissues do not possess fast sodium channels and slow L-t5rpe calcium channels generate phase 0 current (Fig. 12.1). Phase 4 activity varies between nodal areas the sinoatrial node depolarizes more rapidly than the atrioventricular (AV) node. Automaticity is under autonomic nervous system control. Parasympathetic neurons... 

---