Related Experiment Video
Updated: Sep 27, 2026

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Modulation of the hyperpolarization-activated current (I(f)) by calcium and calmodulin in the guinea-pig sino-atrial
Lauren Rigg1, Paul A D Mattick, Bronagh M Heath
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Abstract:
The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (I(f)) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 degrees C) and the perforated patch voltage-clamp technique used to record I(f) activated by hyperpolarizing voltage steps. A 10-min loading of SA node cells with the calcium chelator BAPTA (using 10 microM BAPTA-AM) significantly reduced the amplitude of I(f) at all potentials studied (69+/-8% at -80 mV, n=6). BAPTA loading also shifted the voltage of half-activation (V(h)) of the conductance from -83+/-2 mV in control to -93+/-2 mV in BAPTA (n=6) without significantly altering the slope of activation. The calmodulin antagonists W-7 (10 microM), calmidazolium (25 microM) and ophiobolin A (20 microM) caused similar reductions in I(f) amplitude (73+/-4, 86+/-9 and 59+/-6% at -80 mV, n=6, 5 and 4, respectively) and shifts in V(h) (11+/-3, 14+/-3 and 8+/-2 mV). In cells pre-treated with W-7, exposure to BAPTA caused no further reduction in current amplitude (n=6). I(f) current amplitude was unaffected by the calmodulin dependent kinase (CaMKII) inhibitor KN-93 (1 microM) although this CaMKII inhibition did reduce L-type calcium by 48+/-19% at 0 mV (n=3). These results are consistent with a role for calcium and calmodulin in the regulation of I(f), via a mechanism that is independent of CaMKII. Alterations in intracellular calcium during the cardiac cycle may be involved in fine tuning the voltage-dependent properties of I(f) and may thus determine its relative contribution to pacemaking in the SA node.
More Related Videos
Related Concept Videos
G-Protein Gated Ion Channels
Sensory organs,...
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Electrophysiology of Normal Cardiac Rhythm
Conduction System of the Heart
The pacemaker cells are located in two primary nodes: the sinoatrial (SA) node and the atrioventricular (AV) node. The SA node pacemaker cells can autonomously depolarize, triggering an action potential that leads to the...
Cardiac Action Potential
The cardiac action potential process involves a series of phases characterized by the movement of ions across the cardiac cell membranes, leading to the depolarization and repolarization of the cardiac myocytes.
Ionic Basis of Cardiac Action Potentials

