Cardiac Arrhythmias: Difference between revisions

The cardiac action potential is a result of ions flowing through different ion channels. Ion channels are passages for ions (mainly Na+, K+, Ca2+ and Cl-) that facilitate movement through the cell membrane. Changes in structure of these channels can open, inactivate or close and control current inside and outside the myocytes. Due to different activity and expression of ion channels, the various parts of the cardiac conduction channel have slightly different action potential characteristics. Ion channels are mostly a passive passage, where movement of ions are caused by the electrochemical activity gradient. In addition to these passive ion channels a few ATP-dependent channels exist to fine-tune the action potential. These changes of membrane potential produce and action potential lasting a few hundreds of milliseconds. Disorders is single channels can lead to arrhythmias, as seen in the section genetic arrhythmias (link). The action potential is conducted throughout the heart by the depolarization of the immediate environment of the cells and through intracellular coupling with gap-junctions. The communication pores are located in cell to cell adhesion structures, the intercalated disks.

In summary during the depolarization, sodium ions stream into the cell followed by a influx of Ca2+ ions (both from the inside (sarcoplasmatic reticulum) and outside of the cell). These Ca2+ ions cause the actual muscular contraction. Shortly thereafter K+ ions stream out of the cell. During repolarization the ion concentration returns to its precontraction state. The action potential can be divided in five phases:  

Rapid depolarization is started once the membrane potential reaches a certain threshold (about -70 to -60 mV), independent of the size of the depolarizing stimulus. This produces a rapid influx of Na+ and a rapid upstroke of the action potential. At higher potentials (-40 to -30) Ca2+ influx participates in the upstroke. In sinus node and AV node a slower upstroke can be observed (Figure 1). This caused because the upstroke in these cells are mainly mediated by the slower acting Ca2+ ion channels. The slow activation and inactivation produce a slower upstroke.

Immediately following rapid depolarization, the inactivation of INa and subsequent activation of the outward K+ current ITO and the Na+/Ca2+ exchanger produce a early rapid repolarization. Due to the absence of INa in the upstroke of sinus node and AV node cells and the subsequent slower depolarization, this rapid repolarisation is not visible in their action potentials.

The plateau phase represents an equal influx and efflux of ions producing a stable membrane potential. The influx is mediated by Ca2+ through the open L-type Ca2+ channels and the exchange of Na+ for internal Ca2+ by the Na+/Ca2+ exchanger. The efflux is the result of outward current carried by K+ and Cl- ions.

Final repolarization is mainly caused by inactivation of Ca2+ channels, reducing the influx of positive ions. Furthermore repolarizing K+ currents (delayed rectifier current IKs and IKr and inwardly rectifying current IK1 and IK,Ach) are activated which increase efflux of positive ions. This result in an repolarization to the resting membrane potential.

Depending on cell type the resting membrane potential is between -50 to -95 mV, sinus node and AV nodal cells have a predominately higher resting membrane potential (-50 to -60 mV and -60 to -70 respectively) in comparison with atrial and ventricular cardiomyocytes (-80 to -90 mV). This distribution is mainly caused by the Na+ outside the cell and the K+ inside the cell. Sinus node cells and AV nodal cells (and to a lesser degree Purkinje fibers cells) have a special voltage dependent channel If, the funny current. Furthermore they lack IK1, a K+ current that maintains the resting membrane potential in atrial and ventricular tissue. This channel displays a slow depolarization in diastole, called the phase 4 diastolic depolarization, and results normal automaticity. Sinus node discharges are regulated by the autonomous nerve system and due to its high firing frequency dominates other potential pacemaker sites.

* Delayed afterdepolarizations occur after the cell has recovered after completion of repolarization. In delayed afterdepolarization an abnormal Ca2+ handling of the cell is probably responsible for the afterdepolarizations due to release of Ca2+ from the storage of Ca2+ in the sarcoplasmatic reticulum. The accumulation of Ca2+ increases membrane potential and thus depolarizes the cell when it reaches a certain threshold.

Conduction block or conduction delay is a frequent cause of bradyarrhythmias, however tacharrhythmias can also result from conduction block and produce a reentrant circuit. Conduction block can develop in different conditions, for instance a deceleration block or a acceleration block. These conduction block develop due to deceleration or a slow heart rate or a acceleration or fast heart rate respectively. It is important to assess the cause of conduction block as explained in the section of bradyarrhythmias [link], for it is important in the treatment of the conduction delay or block.