Src family protein tyrosine kinase (PTK) and MAPK are involved in mediating the effect of low potassium intake (LK) on ROMK channels

Abstract

We have previously demonstrated that K‐depletion inhibited ROMK‐like small conductance K channels (SK) in the CCD and that the effect is mediated by superoxide anions which stimulate PTK and MAPK. However, K‐depletion caused a severe hypokalemia. Thus, it is not clear whether PTK and MAPK are also involved in regulating SK channels under physiological conditions. The aim of the present study is to examine whether PTK and MAPK play a physiological role in suppressing SK channel activity in response to LK (0.1%). Rats on LK diet for 7 days have a normal plasma K concentration (control, 4.74 and LK, 4.64 mM). However, LK intake significantly stimulates the production of superoxide by 95% in the renal cortex and outer medulla, and increases the phosphorylation of p38 and ERK and the expression of c‐Src. Also, patch‐clamp experiments have demonstrated that LK intake significantly decreased SK channel activity in the CCD. However, Inhibiting p38 and ERK with SB202190 and PD98059 or blocking PTK with herbimycin A significantly stimulates SK channel activity in the CCD in rats on LK. We conclude that MAPK and Src family PTK play a physiological role in inhibiting SK channels in response to LK intake.