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Membrane currents underlying activity in frog sinus venosus.

H F Brown, W Giles, S J Noble

    The Journal of Physiology
    |October 1, 1977
    PubMed
    Summary
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    Investigating frog heart muscle, this study reveals that pacemaker activity is primarily driven by a slow inward current, insensitive to tetrodotoxin (TTX). This ionic current, along with outward potassium currents, generates the heart's spontaneous electrical rhythm.

    Area of Science:

    • Cardiology
    • Electrophysiology
    • Comparative Physiology

    Background:

    • The sinus venosus of the frog heart (Rana catesbeiana) exhibits spontaneous electrical activity crucial for cardiac pacing.
    • Understanding the ionic mechanisms underlying this pacemaker activity is essential for comprehending cardiac electrophysiology.

    Purpose of the Study:

    • To investigate the ionic currents responsible for pacemaker depolarization and action potential generation in Rana catesbeiana sinus venosus.
    • To classify the nature of the observed pacemaker activity based on its sensitivity to tetrodotoxin (TTX).

    Main Methods:

    • Utilized the double sucrose gap technique for electrophysiological recordings.
    • Employed voltage clamp methods to isolate and analyze ionic currents.
    • Tested the effect of tetrodotoxin (TTX) and manganese ions on ionic currents.

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    Main Results:

    • Pacemaker activity was largely insensitive to tetrodotoxin (TTX), indicating primary pacing.
    • A TTX-insensitive, manganese-sensitive slow inward current (I(si)), likely carried by Ca(2+)/Na(+), was identified and activated near the diastolic potential.
    • Time-dependent outward currents, likely potassium-based, were observed with complex decay kinetics, suggesting multiple components.

    Conclusions:

    • Pacemaker activity in Rana catesbeiana sinus venosus is generated by the interplay of a slow inward current and decaying outward currents.
    • The findings support a model where outward current decay and slow inward current activation drive pacemaker depolarization.
    • Comparison with rabbit sino-atrial node data provides insights into conserved mechanisms of cardiac pacemaking.