The roles of the Na+/K+-ATPase, NKCC, and K+ channels in regulating local sweating and cutaneous blood flow during exercise in humans in vivo

Abstract

Na⁺/K⁺-ATPase has been shown to regulate the sweating and cutaneous vascular responses during exercise; however, similar studies have not been conducted to assess the roles of the Na-K-2Cl co-transporter (NKCC) and K⁺ channels. Additionally, it remains to be determined if these mechanisms underpinning the heat loss responses differ with exercise intensity. Eleven young (24 ± 4 years) males performed three 30-min semirecumbent cycling bouts at low (30% VO_2peak), moderate (50% VO_2peak), and high (70% VO_2peak) intensity, respectively, each separated by 20-min recovery periods. Using intradermal microdialysis, four forearm skin sites were continuously perfused with either: (1) lactated Ringer solution (Control); (2) 6 mmol·L^-1 ouabain (Na⁺/K⁺-ATPase inhibitor); (3) 10 mmol·L^-1 bumetanide (NKCC inhibitor); or (4) 50 mmol·L^-1 BaCl₂ (nonspecific K⁺ channel inhibitor); sites at which we assessed local sweat rate (LSR) and cutaneous vascular conductance (CVC). Inhibition of Na⁺/K⁺-ATPase attenuated LSR compared to Control during the moderate and high-intensity exercise bouts (both P ˂ 0.01), whereas attenuations with NKCC and K⁺ channel inhibition were only apparent during the high-intensity exercise bout (both P ≤ 0.05). Na⁺/K⁺-ATPase inhibition augmented CVC during all exercise intensities (all P ˂ 0.01), whereas CVC was greater with NKCC inhibition during the low-intensity exercise only (P ˂ 0.01) and attenuated with K⁺ channel inhibition during the moderate and high-intensity exercise conditions (both P ˂ 0.01). We show that Na⁺/K⁺-ATPase, NKCC and K⁺ channels all contribute to the regulation of sweating and cutaneous blood flow but their influence is dependent on the intensity of dynamic exercise.

Keywords: NKCC; Exercise; K+ channels; Na+/K+‐ATPase; heat loss; microcirculation; sweat gland.