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PMID:12700358

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Citation

Mangoni, ME, Couette, B, Bourinet, E, Platzer, J, Reimer, D, Striessnig, J and Nargeot, J (2003) Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity. Proc. Natl. Acad. Sci. U.S.A. 100:5543-8

Abstract

The spontaneous activity of pacemaker cells in the sino-atrial node (SAN) controls the heart rhythm and rate under physiological conditions. Pacemaker activity in SAN cells is due to the presence of the diastolic depolarization, a slow depolarization phase that drives the membrane voltage from the end of an action potential to the threshold of a new action potential. SAN cells express a wide array of ionic channels, but we have limited knowledge about their functional role in pacemaker activity and we still do not know which channels play a prominent role in the generation of the diastolic depolarization. It is thus important to provide genetic evidence linking the activity of genes coding for ionic channels to specific alterations of pacemaker activity of SAN cells. Here, we show that target inactivation of the gene coding for alpha(1D) (Ca(v)1.3) Ca(2+) channels in the mouse not only significantly slows pacemaker activity but also promotes spontaneous arrhythmia in SAN pacemaker cells. These alterations of pacemaker activity are linked to abolition of the major component of the L-type current (I(Ca,L)) activating at negative voltages. Pharmacological analysis of I(Ca,L) demonstrates that Ca(v)1.3 gene inactivation specifically abolishes I(Ca,L) in the voltage range corresponding to the diastolic depolarization. Taken together, our data demonstrate that Ca(v)1.3 channels play a major role in the generation of cardiac pacemaker activity by contributing to diastolic depolarization in SAN pacemaker cells.

Links

PubMed PMC154381 Online version:10.1073/pnas.0935295100

Keywords

Action Potentials; Adult; Animals; Base Sequence; Calcium Channels, L-Type/genetics; Calcium Channels, L-Type/physiology; DNA Primers; Humans; Mice; Mice, Knockout; Middle Aged; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Sinoatrial Node/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CAC1D

acts_upstream_of_or_within

GO:0070588: calcium ion transmembrane transport

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2180141

P

  • occurs_in:(CL:1000477)
  • occurs_in:(EMAPA:35772)

Seeded From UniProt

complete

MOUSE:CAC1D

acts_upstream_of_or_within

GO:0086091: regulation of heart rate by cardiac conduction

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2180141

P

  • occurs_in:(EMAPA:35772)

Seeded From UniProt

complete

MOUSE:CAC1D

acts_upstream_of_or_within

GO:0086046: membrane depolarization during SA node cell action potential

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2180141

P

  • occurs_in:(CL:1000477)
  • occurs_in:(EMAPA:35772)

Seeded From UniProt

complete


See also

References

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