Abstract
Atrioventricular node (AV node) is the hub where electrical input from the atria is propagated and conveyed to the ventricles. Despite its strategic position and role in governing impulse conduction between atria and ventricles, there is paucity of data regarding the contribution of specific ion channels to the function of the AV node. Here, we examined the roles of Cav1.3 L-type Ca2+ channel in AV node by taking advantage of a mouse model with null mutation of Cav1.3 (Cav1.3-/-). Cav1.3 null mutant mice show evidence of AV node dysfunction with AV block, suggesting the tissue-specific function of the Cav1.3 channel. In keeping with this assertion, we demonstrate that Cav1.3 isoform is highly expressed in the isolated AV node cells. Furthermore, AV node isolated from Cav1.3 null mutant mice show a significant decrease in the firing frequency of spontaneous action potentials suggesting that Cav1.3 L-type Ca2+ channel plays significant roles in the automaticity of the AV node. Because of the distinct voltage-dependence of Cav1.2 and Cav1.3 Ca2+ channels, Cav1.2 alone does not suffice to maintain normal AV node function. Cav1.3 currents activate at more hyperpolarizing voltage compared to Cav1.2 currents. Consequently, Cav1.2 Ca2+ channel cannot functionally substitute for Cav1.3 isoform in the AV node of Cav1.3 null mutant mice. Thus, our study demonstrates that the distinct biophysical properties of Cav1.3 Ca2+ channel play critical roles in the firing frequency of AV node tissues.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 194-202 |
| Number of pages | 9 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 50 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2011 |
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Keywords
- Atrioventricular nodes
- Cav1.3 channel
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine
Cite this
Expression and roles of Cav1.3 (α1D) L-Type Ca2+ Channel in atrioventricular node automaticity. / Zhang, Qian; Timofeyev, Valeriy; Qiu, Hong; Lu, Ling; Li, Ning; Singapuri, Anil; Torado, Cyril L.; Shin, Hee Sup; Chiamvimonvat, Nipavan.
In: Journal of Molecular and Cellular Cardiology, Vol. 50, No. 1, 01.2011, p. 194-202.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression and roles of Cav1.3 (α1D) L-Type Ca2+ Channel in atrioventricular node automaticity
AU - Zhang, Qian
AU - Timofeyev, Valeriy
AU - Qiu, Hong
AU - Lu, Ling
AU - Li, Ning
AU - Singapuri, Anil
AU - Torado, Cyril L.
AU - Shin, Hee Sup
AU - Chiamvimonvat, Nipavan
PY - 2011/1
Y1 - 2011/1
N2 - Atrioventricular node (AV node) is the hub where electrical input from the atria is propagated and conveyed to the ventricles. Despite its strategic position and role in governing impulse conduction between atria and ventricles, there is paucity of data regarding the contribution of specific ion channels to the function of the AV node. Here, we examined the roles of Cav1.3 L-type Ca2+ channel in AV node by taking advantage of a mouse model with null mutation of Cav1.3 (Cav1.3-/-). Cav1.3 null mutant mice show evidence of AV node dysfunction with AV block, suggesting the tissue-specific function of the Cav1.3 channel. In keeping with this assertion, we demonstrate that Cav1.3 isoform is highly expressed in the isolated AV node cells. Furthermore, AV node isolated from Cav1.3 null mutant mice show a significant decrease in the firing frequency of spontaneous action potentials suggesting that Cav1.3 L-type Ca2+ channel plays significant roles in the automaticity of the AV node. Because of the distinct voltage-dependence of Cav1.2 and Cav1.3 Ca2+ channels, Cav1.2 alone does not suffice to maintain normal AV node function. Cav1.3 currents activate at more hyperpolarizing voltage compared to Cav1.2 currents. Consequently, Cav1.2 Ca2+ channel cannot functionally substitute for Cav1.3 isoform in the AV node of Cav1.3 null mutant mice. Thus, our study demonstrates that the distinct biophysical properties of Cav1.3 Ca2+ channel play critical roles in the firing frequency of AV node tissues.
AB - Atrioventricular node (AV node) is the hub where electrical input from the atria is propagated and conveyed to the ventricles. Despite its strategic position and role in governing impulse conduction between atria and ventricles, there is paucity of data regarding the contribution of specific ion channels to the function of the AV node. Here, we examined the roles of Cav1.3 L-type Ca2+ channel in AV node by taking advantage of a mouse model with null mutation of Cav1.3 (Cav1.3-/-). Cav1.3 null mutant mice show evidence of AV node dysfunction with AV block, suggesting the tissue-specific function of the Cav1.3 channel. In keeping with this assertion, we demonstrate that Cav1.3 isoform is highly expressed in the isolated AV node cells. Furthermore, AV node isolated from Cav1.3 null mutant mice show a significant decrease in the firing frequency of spontaneous action potentials suggesting that Cav1.3 L-type Ca2+ channel plays significant roles in the automaticity of the AV node. Because of the distinct voltage-dependence of Cav1.2 and Cav1.3 Ca2+ channels, Cav1.2 alone does not suffice to maintain normal AV node function. Cav1.3 currents activate at more hyperpolarizing voltage compared to Cav1.2 currents. Consequently, Cav1.2 Ca2+ channel cannot functionally substitute for Cav1.3 isoform in the AV node of Cav1.3 null mutant mice. Thus, our study demonstrates that the distinct biophysical properties of Cav1.3 Ca2+ channel play critical roles in the firing frequency of AV node tissues.
KW - Atrioventricular nodes
KW - Cav1.3 channel
UR - http://www.scopus.com/inward/record.url?scp=78650822557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650822557&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2010.10.002
DO - 10.1016/j.yjmcc.2010.10.002
M3 - Article
C2 - 20951705
AN - SCOPUS:78650822557
VL - 50
SP - 194
EP - 202
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
IS - 1
ER -