Cardiac action potential inward rectifier

Inward Rectifier K+ Channels. Figure 1 The role of inward rectifier (Kir) channels in cardiac action potentials. Depolarization is generated and maintained by Na and Ca currents (/Na, /Ca). Voltage-gated K currents (Kv) and Kir channels contribute to repolarization and maintenance of a negative resting potential. 

Other potassium channels also play important roles here. For example, Kv4.3/ KChIP complex conducts the transient outward current, Ito, responsible for the descending phase 1 of the cardiac action potential, whereas Kvl.5 is underlying the ultra rapid delayed rectifying current, IKur, responsible for descending phase 2. Finally, inward rectifier potassium channel (Kir2 family) is responsible for IKl current, which maintains the action potential close to or at the resting level (phase 4). 

Activation Atrial preparation Biophysics Calcium channel Cardiac action potential Channel kinetics Comprehensive in vitro proarrhythmia assay Delayed rectifier Early afterdepolarisation ECG Hodgkin-Huxley ICHS7A ICHS7B In silico modelling Inactivation Inward rectifier Langendorff heart Purkinje fibre Safety assessment Sodium channel Stem cells... 

Cardiac APD is controlled by a fine balance between inward and outward currents in the repolarization phase. Since outward K+ currents, especially the delayed rectifier repolarizing current, IK (which is the sum of two kinetically and pharmacologically distinct types of K+ currents a rapid, 1k and a slow, IKs, component), play an important role during repolarization and in determining the configuration of the action potential, small changes in conductance can significantly alter the effective refractory period, hence the action potential duration. 

Ibutilide prolongs action potential in isolated adult cardiac myocytes and increases both atrial and ventricular refractoriness in vivo. An additional action is blockade of outward potassium currents. Thus, ibutilide acts by blocking the rapid component of the delayed rectifier current (IKr) as well as by activation of a slow inward current carried predominantly by sodium. 

Similar to the mouse ES model, wholecell patch-clamp studies showed that the hES cell-derived cardiomyocytes also display cardiac-specific action potential morphologies and ion currents (Fig. 12.2) [55]. Additional studies conducted in our laboratory revealed the basis for the spontaneous automaticity in these cells, at least at the mid-differentiation stages. These studies revealed that during this stage, the spontaneous electrical activity is mediated by the absence of significant inward rectifier current and a prominent Na current sensitive to TTX coupled with the... 

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