Pacemaker current (If) in the human sinoatrial node

Aims Animal studies revealed that the hyperpolarization-activated pacemaker current, If, contributes to action potential (AP) generation in sinoatrial node (SAN) and significantly determines heart rate. If is becoming a novel therapy target to modulate heart rate. Yet, no studies have demonstrated t...

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Bibliographic Details
Published in:European heart journal 2007-10, Vol.28 (20), p.2472-2478
Main Authors: Verkerk, Arie O., Wilders, Ronald, van Borren, Marcel M.G.J., Peters, Ron J.G., Broekhuis, Eli, Lam, Kayan, Coronel, Ruben, de Bakker, Jacques M.T., Tan, Hanno L.
Format: Article
Language:English
Subjects:
Action potentials
Action Potentials - physiology
Biological and medical sciences
Cardiology. Vascular system
Electrophysiology
Female
Follow-Up Studies
Heart Conduction System - cytology
Heart Conduction System - physiology
Humans
Ion channels
Ion Channels - physiology
Medical sciences
Middle Aged
Pacing
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Sinoatrial node
Sinoatrial Node - cytology
Sinoatrial Node - physiology
Sinoatrial Node - surgery
Tachycardia, Paroxysmal - physiopathology
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Summary:Aims Animal studies revealed that the hyperpolarization-activated pacemaker current, If, contributes to action potential (AP) generation in sinoatrial node (SAN) and significantly determines heart rate. If is becoming a novel therapy target to modulate heart rate. Yet, no studies have demonstrated that If is functionally present and contributes to pacemaking in human SAN. We aimed to study If properties in human SAN. Methods and results In a patient undergoing SAN excision, we identified SAN using epicardial activation mapping. From here, we isolated myocytes and recorded APs and If using patch-clamp techniques. Pacemaker cells generated spontaneous APs (cycle length 828 ± 15 ms) following slow diastolic depolarization, maximal diastolic potential − 61.7 ± 4.3 mV, and maximal AP upstroke velocity 4.6 ± 1.2 V/s. They exhibited an hyperpolarization-activated inward current, blocked by external Cs+ (2 mmol/L), characterizing it as If. Fully-activated conductance was 75.2 ± 3.8 pS/pF, reversal potential − 22.1 ± 2.4 mV, and half-maximal activation voltage and slope factor of steady-state activation − 96.9 ± 2.7 and − 8.8 ± 0.5 mV. Activation time constant ranged from ∼350 ms (−130 mV) to ∼1 s (−100 mV), deactivation time constant 156 ± 45 ms (−40 mV). The role of If in pacemaker activity was demonstrated by slowing of pacemaker cell diastolic depolarization and beating rate by Cs+. Conclusion If is functionally expressed in human SAN and probably contributes to pacemaking in human SAN.
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehm339