Na+ currents are required for efficient excitation-contraction coupling in rabbit ventricular myocytes: a possible contribution of neuronal Na+ channel to triggering Ca2+ release from the Sarcoplasmic Reticulum.
Summary of "Na+ currents are required for efficient excitation-contraction coupling in rabbit ventricular myocytes: a possible contribution of neuronal Na+ channel to triggering Ca2+ release from the Sarcoplasmic Reticulum."
Ca2+ transients were activated in rabbit ventricular cells by a sequence of action potential shaped voltage clamps. After activating a series of control transients, Na+ currents (INa) were inactivated with a ramp from -80 to 40 mV (1.5 s) prior to the action potential clamp. The transients were detected with the calcium indicator Fluo-4 and an epifluorescence system. With zero Na+ in the pipette INa inactivation produced a decline in the SR Ca2+ release flux (measured as the maximum rate of rise of the transient) of 27±4% (n=9, P<0.001) and a peak amplitude reduction of 10±3% (n=9, P<0.05). With 5 mM Na+ in the pipette the reduction in release flux was greater (34±4%, n=4, P<0.05). The ramp effectively inactivates INa without changing ICa, and there was no significant change in the transmembrane Ca2+ flux after the inactivation of INa. We next evoked action potentials under current clamp. 100 nM TTX, which selectively blocks neuronal isoforms of Na+ channels, produced a decline in SR Ca2+ release flux of 35±3% (n=6, P<0.001) and transient amplitude of 12±2% (n=6, P<0.05). This effect was similar to the effect of INa inactivation on release flux. We conclude that a TTX-sensitive INa is essential for efficient triggering SR Ca2+ release. We propose that neuronal Na+ channels residing within couplons activate sufficient reverse NCX to prime the junctional cleft with Ca2+. With non-linearities in the excitation-contraction coupling mechanism could increase the coupling fidelity of ICa, which is known to be very low at positive potentials.
Affiliation
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah;
Journal Details
This article was published in the following journal.
Name: The Journal of physiology
ISSN: 1469-7793
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20837647
- DOI: http://dx.doi.org/10.1113/jphysiol.2010.194688
Medical and Biotech [MESH] Definitions
Excitation Contraction Coupling
A process fundamental to muscle physiology whereby an electrical stimulus or action potential triggers a myocyte to depolarize and contract. This mechanical muscle contraction response is regulated by entry of calcium ions into the cell.
Fendiline
Coronary vasodilator; inhibits calcium function in muscle cells in excitation-contraction coupling; proposed as antiarrhythmic and antianginal agents.
Dantrolene
Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants.
Ryanodine Receptor Calcium Release Channel
A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.
Pre-excitation, Mahaim-type
A form of ventricular pre-excitation characterized by a normal PR interval and a long QRS interval with an initial slow deflection (delta wave). In this syndrome, the atrial impulse travel to the ventricle via the Mahaim fibers which connect ATRIOVENTRICULAR NODE directly to the right ventricle wall (nodoventricular pathway) or to the RIGHT BUNDLE BRANCH OF HIS (nodofascicular pathway).
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