Regulation of cardiac Ca(2+) channel by extracellular Na(+)

Cell Calcium. 2011 Mar;49(3):162-73. doi: 10.1016/j.ceca.2011.01.008. Epub 2011 Feb 23.


Hyponatremia is a predictor of poor cardiovascular outcomes during acute myocardial infarction and in the setting of preexisting heart failure [1]. There are no definitive mechanisms as to how hyponatremia suppresses cardiac function. In this report we provide evidence for direct down-regulation of Ca(2+) channel current in response to low serum Na(+). In voltage-clamped rat ventricular myocytes or HEK 293 cells expressing the L-type Ca(2+) channel, a 15mM drop in extracellular Na(+) suppressed the Ca(2+) current by ∼15%; with maximal suppression of ∼30% when Na(+) levels were reduced to 100mM or less. The suppressive effects of low Na(+) on I(Ca), in part, depended on the substituting monovalent species (Li(+), Cs(+), TEA(+)), but were independent of phosphorylation state of the channel and possible influx of Ca(2+) on Na(+)/Ca(2+) exchanger. Acidification sensitized the Ca(2+) channel current to Na(+) withdrawal. Collectively our data suggest that Na(+) and H(+) may interact with regulatory site(s) at the outer recesses of the Ca(2+) channel pore thereby directly modulating the electro-diffusion of the permeating divalents (Ca(2+), Ba(2+)).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium Channel Agonists / pharmacology
  • Calcium Channels, L-Type / chemistry
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Electrophysiological Phenomena
  • HEK293 Cells
  • Humans
  • Male
  • Myocytes, Cardiac / metabolism*
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sodium / metabolism*
  • Sodium-Calcium Exchanger / metabolism


  • Calcium Channel Agonists
  • Calcium Channels, L-Type
  • Recombinant Proteins
  • Sodium-Calcium Exchanger
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Sodium
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium