Redistribution of Myosin VI from Top to Base of Proximal Tubule Microvilli during Acute Hypertension

Abstract

During acute hypertension, Na⁺/H⁺ exchangers (NHE3) retract from top to base of proximal tubule microvilli (MV) and Na⁺ reabsorption decreases in proximal tubule. This study aimed to determine whether the actin-based motor myosin VI coordinately retracts with NHE3 in response to acute hypertension. BP was raised approximately 50 mmHg in rats for 20 to 30 min or sham treated, and kidneys were analyzed by subcellular fractionation or microscopy. During acute hypertension, myosin VI redistributed from low density apical MV-enriched membranes (from 23 ± 2.4 to 11.4 ± 2.2%) into higher density membranes (from 23.2 ± 0.7 to 36.9 ± 2.6%). By confocal microscopy, myosin VI was detected over the whole length of the MV in controls, then became completely focused at the base of MV during acute hypertension. For electron microscopic analysis using immunogold labeling, MV were divided into five zones from top (z1) to base (z5). In controls, myosin VI was evenly distributed through the five MV zones. In acute hypertension, myosin VI decreased in z1 (from 20.6 ± 1.9 to 10.5 ± 2.3%) and z2 (from 21.0 ± 2.0 to 13.2 ± 1.4%) and increased in z5 (from 21.1 ± 3.3 to 38.6 ± 3.0%). These results provide the first observation that acute hypertension causes myosin VI redistribution and support the idea that myosin VI may serve as the molecular motor for NHE3 retraction from top to base of MV during acute hypertension.