Function
The funny current is highly expressed in spontaneously active cardiac regions, such as the sinoatrial node (SAN, the natural pacemaker region), the atrio-ventricular node (AVN) and the Purkinje fibres of conduction tissue. Particularly unusual, the funny current is a mixed sodium-potassium current, inward and slowly activating on 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 current is activated and supplies inward current, which is responsible for starting the diastolic depolarization phase (DD); by this mechanism, the funny current controls the rate of spontaneous activity of sinoatrial myocytes, hence 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 current 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.
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