Chronic or sustained changes in pump activity within cells is usually due to increases in transcription rate or mRNA stability. This effect appears to result from stimulation of subunit gene transcription. Aldosterone is a steroid hormone with major effects on sodium homeostasis. It stimulates both rapid and sustained increases in pump numbers within several tissues. The sustained effect is due to enhanced transcription of the genes for both subunits.
Catecholamines have varied effects, depending on the specific hormone and tissue.
These effects seem to be mediated via phosphorylation or dephosphorylation of the pumps. Insulin is a major regulator of potassium homeostasis and has multiple effects on sodium pump activity. Within minutes of elevated insulin secretion, pumps containing alpha-1 and 2 isoforms have increased affinity for sodium and increased turnover rate. Sustained elevations in insulin causes upregulation of alpha-2 synthesis. In skeletal muscle, insulin may also recruit pumps stored in the cytoplasm or activate latent pumps already present in the membrane.