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Published on: July 3, 2013
Molecular and electrophysiological differences in the L-type Ca2+ channel of the atrium and ventricle of rat hearts
Seiji Hatano1, Takeshi Yamashita, Akiko Sekiguchi
1The Cardiovascular Institute, Tokyo, Japan. shatano-circ@umin.ac.jp
Background:
Many pathological conditions induce electrical remodeling, possibly through intracellular Ca2+ overload, but the currently available L-type Ca2+ channel blockers may be detrimental because of their global negative inotropic effects.
Methods And Results:
To determine whether the L-type Ca2+ channel is identical throughout the heart, the distribution of the mRNAs and proteins comprising the L-type Ca2+ channel and its electrophysiological properties were analyzed in rat atria and ventricles. The mRNA of alpha2delta-2 (Cacna2d2) was more abundantly expressed in the atrium (approximately 5-fold) than in the ventricle. In contrast, alpha1C (Cacna1c) (Cav1.2) mRNA was significantly less abundant in the atrium. The level of the alpha1C (Cacna1c) (Cav1.2) protein was decreased (approximately 0.5-fold) and that of alpha2 delta-1 (Cacna2d1) was increased (approximately 2-fold) in the atrium compared with the ventricle. Although the peak ICa,L density showed no significant differences, voltage dependence of inactivation and activation of the current showed a more depolarized shift in the atrium than in the ventricle.
Conclusion:
These results indicate that in the rat heart the L-type Ca2+ channel differs between the atrium and ventricle with regard to gene expression and electrophysiological properties.
Insights
The L-type Ca2+ channel in rat hearts shows distinct gene expression and electrical properties between atria and ventricles. This difference may impact targeted therapies for cardiac conditions.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Ion Channel Biology
Background:
- Pathological conditions can cause cardiac electrical remodeling via intracellular Ca2+ overload.
- Current L-type Ca2+ channel blockers may have adverse effects due to global negative inotropic actions.
Purpose of the Study:
- To investigate if L-type Ca2+ channels are uniform across the rat heart.
- To analyze the distribution and properties of L-type Ca2+ channel components in atria and ventricles.
Main Methods:
- Analysis of mRNA and protein expression of L-type Ca2+ channel subunits (alpha2delta-2, alpha1C/Cav1.2, alpha2delta-1).
- Electrophysiological characterization of the L-type Ca2+ current (ICa,L) in rat atria and ventricles.
Main Results:
- Alpha2delta-2 (Cacna2d2) mRNA was 5-fold higher in atria than ventricles.
- Alpha1C (Cacna1c/Cav1.2) mRNA and protein levels were lower in atria compared to ventricles.
- Atrial ICa,L exhibited a depolarized shift in activation and inactivation compared to ventricular ICa,L, despite similar peak current density.
Conclusions:
- Significant differences exist in L-type Ca2+ channel gene expression between rat atria and ventricles.
- Electrophysiological properties of L-type Ca2+ channels also vary between these cardiac regions.
- These regional differences are crucial for understanding cardiac electrophysiology and developing targeted channel blockers.
