In neonatal myocytes grown in culture, reductions in extracellular potassiu
m concentration produced a hypertrophic response as assessed by induction o
f early response genes, atrial natriuretic peptide and skeletal actin, and
repression of the alpha 3 isoform of the sodium pump in a dose dependent ma
nner. The degree of alpha 3 repression appeared to be dose dependent with d
ecreases in media (K). Similarly, decreases in media potassium concentratio
ns caused increases in cytosolic calcium concentration in a dose dependent
manner; moreover these increases in cytosolic calcium concentration correla
ted quite well with repression of alpha 3 expression. In contrast, although
moderate reductions of potassium concentration induced upregulation of skA
CT and ANP, severely reduced potassium concentrations caused repression of
skACT and ANP expression.
In parallel studies performed in vivo, 3-5 weeks dietary K restriction indu
ced molecular phenotypical changes similar to that seen in the neonatal myo
cyte model without demonstrable growth as assessed by the heart weight/body
weight ratio. However, when rates subjected to dietary K restriction were
subsequently subjected to acute aortic constriction, cardiac growth was gre
ater than in rats fed a control diet.
These data suggest that hypokalemia may produce molecular phenotypic altera
tions consistent with cardiac hypertrophy as well as contribute to hypertro
phy in an in vivo model.