Related Experiment Videos
Phosphorylation shifts the time-dependence of cardiac Ca++ channel gating currents
1Department of Physiology and Biophysics, University of Cincinnati, College of Medicine, Ohio 45267-0576.
Abstract:
A general mechanism for the physiological regulation of the activity of voltage-dependent Na+, Ca++, K+, and Cl channels by neurotransmitters in a variety of excitable cell types may involve a final common pathway of a cyclic AMP-dependent phosphorylation of the channel protein. The functional correlates of channel phosphorylation are known to involve a change in the probability of opening, and a negative or positive shift in the voltage dependence for activation of the conductance. The voltage dependence for activation appears to be governed by the properties of the charge movement of the voltage-sensing moiety of the channel. This study of the gating charge movement of cardiac Ca++ channels has revealed that isoproterenol or cAMP (via a presumed phosphorylation of the channel) speeds the kinetics of the Ca++ channel gating charge movement. These results suggest that the changes in the kinetics and voltage dependence of the cardiac calcium currents produced by beta-adrenergic stimulation are initiated, in part, by parallel changes in the gating charge movement.
Insights
Neurotransmitters regulate ion channels via cyclic AMP-dependent phosphorylation. This study shows beta-adrenergic stimulation speeds cardiac calcium channel gating charge movement, suggesting a mechanism for altered calcium currents.
Area of Science:
- Neuroscience
- Molecular Biology
- Cardiology
Background:
- Neurotransmitters physiologically regulate ion channel activity through cyclic AMP-dependent phosphorylation.
- Channel phosphorylation alters opening probability and voltage dependence.
- Voltage dependence is governed by the channel's voltage-sensing moiety charge movement.
Purpose of the Study:
- To investigate the effect of beta-adrenergic stimulation on cardiac calcium channels.
- To elucidate the role of gating charge movement in altered calcium channel kinetics and voltage dependence.
Main Methods:
- Studied the gating charge movement of cardiac Ca++ channels.
- Applied isoproterenol and cAMP to induce channel phosphorylation.
Main Results:
- Isoproterenol or cAMP significantly speeds the kinetics of Ca++ channel gating charge movement.
- These kinetic changes in charge movement correlate with observed changes in cardiac calcium currents.
Conclusions:
- Beta-adrenergic stimulation initiates changes in cardiac calcium currents partly through parallel alterations in gating charge movement.
- Phosphorylation of cardiac calcium channels by beta-adrenergic agents affects their gating charge kinetics.