The funny<unk>  is highly expressed in spontaneously active cardiac regions, such as the sinoatrial node (SAN, the natural<unk>  region), the atrioventricular node (AVN) and the Purkinje fibres of conduction tissue. The funny<unk>  is a mixed sodium–potassium<unk>  that activates upon hyperpolarization at voltages in the diastolic range (normally from −60/−70 mV to −40 mV). When, at the end of a sinoatrial action potential, the membrane repolarizes below the If threshold (about −40/−50 mV), the funny<unk>  is activated and supplies inward<unk> , which is responsible for starting the diastolic depolarization phase (DD); by this mechanism, the funny<unk>  controls the rate of spontaneous activity of sinoatrial myocytes, and thus the cardiac rate. Another unusual feature of If is its dual activation by voltage and by cyclic nucleotides. Cyclic adenosine monophosphate (cAMP) molecules bind directly to f-channels and increase their open probability. cAMP dependence is a particularly relevant physiological property, since it underlies the If-dependent autonomic regulation of heart rate. Sympathetic stimulation raises the level of cAMP-molecules which bind to f-channels and shift the If activation range to more positive voltages; this mechanism leads to an increase of the<unk>  at diastolic voltages and therefore to an increase of the steepness of DD and heart rate acceleration. Parasympathetic stimulation (which acts to increase probability of potassium channels opening but decreases the probability of calcium channel opening) decreases the heart rate by the opposite action, that is by shifting the If activation curve towards more negative voltages. When vagally-released acetylcholine (ACh) binds to muscarinic M2 receptors, which promotes dissociation of βγ subunit complexes, leading to direct opening of the G-protein–gated inwardly rectifying K+ channel (Girk/Kir) IKACh.
Pacemaker current
Cardiac action potential
VA conduction
QRS complex
End-plate potential
QT interval
QT interval variability
PR interval