[Ion channels and arrhythmias].
Changes in ionic currents through ion channels of the myocardial cell membrane have to be regarded as main cause of cardiac arrhythmias. Three basic arrhythmogenic mechanisms are responsible for the initiation of tachyarrhythmias: 1. The disturbance of normal automaticity in cardiac pacemaker cells dependent on the currents If, ICa-L, ICa-T or IK-ACh,Ado and the occurrence of abnormal automaticity in atrial and ventricular working myocardium based on the currents ICa-L, INa, IK, IK1 or IK-ACh,Ado. 2. Triggered activity which may be recognized by the appearance of early (EAD) or late afterdepolarizations (LAD). EAD are mainly due to inhibition of the outward currents IKr and IKs and are favoured by an increase in the inward currents INa and ICa-L, respectively. Typical arrhythmias are torsade de pointes occurring during treatment with K(+)-channel inhibitors (e.g. sotalol) or in patients with QT-syndrome. LAD may be observed during Ca(2+)-overload of the myocardial cell (digitalis intoxication, catecholamines) and are based on the transient inward current Iti, which is build up by the participation of the currents INa/Ca, INS and ICa-L. 3. Reentry mechanisms are the most frequent cause of tachyarrhythmias. They originate in an anatomically defined excitation circle with unidirectional block. Na(+)- and Ca(2+)-channel dependent disturbances of conduction with long excitable gap may be distinguished from Na(+)-channel dependent disturbances of conduction and refractory period with short excitable gap. Interruption of reentry is possible in the first case by depression of conduction and excitability (Na(+)- or Ca(2+)-channel blockers), in the second case by increase in refractory period (K(+)- or Na(+)-channel blockers).
Borchard
U
U
Heinrich-Heine-Universität Düsseldorf, Institut für Pharmakologie, Düsseldorf.
Hafner
D
D
D000200:Action Potentials / Q000502:physiology; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology; D001282:Atrial Flutter / Q000209:etiology / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D005117:Cardiac Complexes, Premature / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013015:Sotalol / Q000009:adverse effects / Q000627:therapeutic use; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology; D016171:Torsades de Pointes / Q000139:chemically induced / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013015:Sotalol