Funny current: pacemaker current or If current
Abstract: The funny current or pacemaker current is predominantly a feature of the sinoatrial node.
Diastolic or phase 4 depolarization is the hallmark of pacemaker cells of the heart. The funny current or pacemaker current is seen mostly in the SA (sinoatrial node) and has been designated as If . If pacemaker current was discovered by Professor D. DiFrancesco in 1979.1 It is a mixed sodium-potassium current which is inward and gets activated on hyperpolarization at voltages of -40 to -45 millivolts.2 The funny current initially opposes the repolarization and then stops it. After that the funny current is responsible for the spontaneous diastolic depolarization which ultimately leads to the automaticity of the sinus node.3 Since the funny current controls the rate of the sinus node activity, it determines the heart rate. If increases on perfusion with adrenaline and thereby the slope of diastolic depolarization and the heart rate.1 Same effect is noted with beta adrenergic stimulation, the effect of which is mediated by cyclic AMP.4 In addition to the diastolic voltage, the funny current activation is also dependent on cyclic AMP and hence can be modulated by the autonomic nervous system. Parasympathetic stimulation which has the opposite effect of beta adrenergic stimulation, can inhibit the funny current.5 This would explain the sinus bradycardia associated with vagotonia.
HCN channel (hyperpolarization activated cyclic nucleotide) mediates the funny current (If). Four types of HCN channels (HCN 1-4) are known at present. HCN4 mutations have been implicated in sinus node dysfunction.
Though the funny current has been described over a quarter of a century back, it has come into attention recently due to the availability of selective If current blockers like ivabradine, a pure sinus node inhibitor without any other hemodynamic effect. Zatebradine and cilobradine are two analogues. A similar Ih current has been described in different types of neurons. If current has also been targeted in the development of a potential biological pacemaker.6
- Brown HF, DiFrancesco D, Noble SJ. How does adrenaline accelerate the heart? Nature. 1979; 280: 235-236.
- DiFrancesco D. A new interpretation of the pace-maker current in calf Purkinje fibres. J Physiol. 1981; 314: 359-376.
- DiFrancesco D. The role of the funny current in pacemaker activity. Circ Res. 2010 Feb 19;106(3):434-46.
- DiFrancesco D, Tortora P. Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature. 1991; 351: 145–147.
- DiFrancesco D, Tromba C. Inhibition of the hyperpolarization-activated current (If) induced by acetylcholine in rabbit sino-atrial node myocytes. J Physiol. 1988; 405: 477-491.
- Rajesh G, Francis J. Biological pacemakers. Indian Pacing Electrophysiol J. 2006 Jan 1;6(1):1-5.