K+‐Induced Dilation of Hamster Cremasteric Arterioles Involves Both the Na+/K+‐ATPase and Inward‐Rectifier K+ Channels

Abstract

Objective: The mechanism by which elevated extracellular potassium ion concentration ([K⁺]_o) causes dilation of skeletal muscle arterioles was evaluated. Methods: Arterioles (n = 111) were hand-dissected from hamster cremaster muscles, cannulated with glass micropipettes and pressurized to 80 cm H₂O for in vitro study. The vessels were superfused with physiological salt solution containing 5 mM KCl, which could be rapidly switched to test solutions containing elevated [K⁺]_o and/or inhibitors. The authors measured arteriolar diameter with a computer-based diameter tracking system, vascular smooth muscle cell membrane potential with sharp micropipettes filled with 200 mM KCl, and changes in intracellular Ca^{2 +} concentration ([Ca^{2 +}]_i) with Fura 2. Membrane currents and potentials also were measured in enzymatically isolated arteriolar muscle cells using patch clamp techniques. The role played by inward rectifier K⁺ (K_IR) channels was tested using Ba^{2 +} as an inhibitor. Ouabain and substitution of extracellular Na⁺ with Li⁺ were used to examine the function of the Na⁺/K⁺ ATPase. Results: Elevation of [K⁺]_o from 5 mM up to 20 mM caused transient dilation of isolated arterioles (27 ± 1 μ m peak dilation when [K⁺]_o was elevated from 5 to 20 mM, n = 105, p < .05). This dilation was preceded by transient membrane hyperpolarization (10 ± 1 mV, n = 23, p < .05) and by a fall in [Ca^{2 +}]_i as indexed by a decrease in the Fura 2 fluorescence ratio of 22 ± 5% (n = 4, p < .05). Ba^{2 +} (50 or 100 μ M) attenuated the peak dilation (40 ± 8% inhibition, n = 22) and hyperpolarization (31 ± 12% inhibition, n = 7, p < .05) and decreased the duration of responses by 37 ± 11% (n = 20, p < 0.05). Both ouabain (1 mM or 100 μM) and replacement of Na⁺ with Li⁺ essentially abolished both the hyperpolarization and vasodilation. Conclusions: Elevated [K⁺]_o causes transient vasodilation of skeletal muscle arterioles that appears to be an intrinsic property of the arterioles. The results suggest that K⁺-induced dilation involves activation of both the Na⁺/K⁺ ATPase and K_IR channels, leading to membrane hyperpolarization, a fall in [Ca^{2 +}]_i, and culminating in vasodilation. The Na⁺/K⁺ ATPase appears to play the major role and is largely responsible for the transient nature of the response to elevated [K⁺]_o, whereas K_IR channels primarily affect the duration and kinetics of the response.