Format

Send to:

Choose Destination
See comment in PubMed Commons below
Eur Heart J. 2007 Oct;28(20):2472-8. Epub 2007 Sep 6.

Pacemaker current (I(f)) in the human sinoatrial node.

Author information

  • 1Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Abstract

AIMS:

Animal studies revealed that the hyperpolarization-activated pacemaker current, I(f), contributes to action potential (AP) generation in sinoatrial node (SAN) and significantly determines heart rate. I(f) is becoming a novel therapy target to modulate heart rate. Yet, no studies have demonstrated that I(f) is functionally present and contributes to pacemaking in human SAN. We aimed to study I(f) 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 I(f) 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 I(f). 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 approximately 350 ms (-130 mV) to approximately 1 s (-100 mV), deactivation time constant 156 +/- 45 ms (-40 mV). The role of I(f) in pacemaker activity was demonstrated by slowing of pacemaker cell diastolic depolarization and beating rate by Cs(+).

CONCLUSION:

I(f) is functionally expressed in human SAN and probably contributes to pacemaking in human SAN.

PMID:
17823213
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk