Modest dietary [K.sup.+] restriction provokes insulin resistance of cellular [K.sup.+] uptake and phosphorylation of renal outer medulla [K.sup.+] channel without fall in plasma [K.sup.+] concentration

Extracellular [K.sup.+] concentration ([[K.sup.+]]) is closely regulated by the concerted regulatory responses of kidney and muscle. In this study, we aimed to define the responses activated when dietary [K.sup.+] was moderately reduced from a control diet (1.0% [K.sup.+]) to a 0.33% [K.sup.+] diet for 15 days. Although body weight and baseline plasma [[K.sup.+]] (4.0 mM) were not reduced in the 0.33% [K.sup.+] group, regulatory responses to conserve plasma [[K.sup.+]] were evident in both muscle and kidney. Insulin- stimulated clearance of [K.sup.+] from the plasma was estimated in vivo in conscious rats with the use of tail venous and arterial cannulas. During infusion of insulin*(50 mU*[kg.sup.-1] * [min.sup.-1]), plasma [[K.sup.+]] level fell to 3.2 [+ or -] 0.1 mM in the 1.0% [K.sup.+] diet group and to only 3.47 [+ or -] 0.07 mM in the 0.33% [K.sup.+] diet group (P < 0.01) with no reduction in urinary [K.sup.+] excretion, which is evidence of insulin resistance to cellular [K.sup.+] uptake. Insulinstimulated cellular [K.sup.4] uptake was quantitated by measuring the [K.sup.+] infusion rate necessary to clamp plasma [K.sup.+] at baseline (in [micro] mol * [kg.sup.-1] * [min.sup.-1]) during 5 mU of insulin * [kg.sup.-1] * [min.sup.-1 infusion: 9.7 [+ or -] 1.5 in 1% [K.sup.+] diet was blunted to 5.2 [+ or -] 1.7 in the 0.33% [K.sup.+] diet group (P < 0.001). Muscle [[K.sup.+]] and [Na.sup.+]-[K.sup.+]-ATPase activity and abundance were unchanged during the 0.33% [K.sup.+] diet. Renal excretion, which was measured overnight in metabolic cages, was reduced by 80%, from 117.6 [+ or -] 10.5 [micro]mol/h/animal (1% [K.sup.+] diet)to 24.2 [+ or -] 1.7 [micro]mol/h/animal (0.33% [K.sup.+] diet) (P < 0.001). There was no significant change in total abundance of key renal [K.sup.+] transporters, but 50% increases in both renal PTK cSrc abundance and ROMK phosphorylation in the 0.33% [K.sup.+] vs. 1% [K.sup.+] diet group, previously established to be associated with internalization of ROMK. These results indicate that plasma [[K.sup.+]] can be maintained during modest K restriction due to a decrease in insulin-stimulated cellular [K.sup.+] uptake as well as renal [K.sup.+] conservation mediated by inactivation of ROMK, both without a detectable change in plasma [[K.sup.+]]. The error signals inciting and maintaining these responses remain to be identified. potassium homeostasis; [Na.sup.+]-[K.sup.+]-ATPase; [H.sup.+]- [K.sup.+]- ATPase; protein tyrosine kinase; cSrc