ATP‐Sensitive K+ Channels in Smooth Muscle Cells from Rat Mesenteric Lymph Vessels VESSELS

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The ATP‐sensitive potassium (KATP) channel is expressed in plasma membranes of many types of smooth muscle cells (SMCs). It is disinhibited when intracellular ATP concentrations are reduced during conditions of metabolic stress, and the resulting K+ efflux through KATP channels mediates membrane hyperpolarization and SMC relaxation. However, in the lymphatic smooth muscle cells (LSMCs) of rhythmically contracting lymphatic vessels, KATP channels reportedly play an important role in regulating the basal rhythmic contractions that establish lymph flow even in the absence of overt metabolic challenge. The KATP channels in LSMCs also may participate in the dilator responses of lymphatic vessels (LVs) to nitric oxide, inflammatory mediators, and compromise lymph flow in other pathologies associated with oxidative stress1,2,3. Although it is recognized that the properties and the subunit composition of KATP channels show tissue‐specificity, the identity and properties of KATP channels in LSMCs are unknown. The goal of this study was to begin to define the function and properties of KATP channels in rat mesenteric LVs. Isolated rat mesenteric LVs were cannulated on glass pipettes, pressurized at 4.5–6 mmHg, and edge detection was used to continuously monitor changes in vessel diameter. Addition of the KATP channel agonist cromakalim (0.01 μM‐100 μM; half‐log units) progressively increased LV diameter and abolished rhythmic contractions (n=3). In contrast, addition of the KATP channel antagonist, glibenclamide (0.01 μM‐100 μM; half‐log units) resulted in no change in LV diameter but suppressed rhythmic contractions. The latter finding confirmed the important role of KATP channels as regulators of LV contractile function under basal conditions. Subsequently, we have begun to characterize KATP channel currents in SMCs freshly isolated from rat mesenteric LVs. Patch‐clamp studies in the cell‐attached mode reveal unitary K+ currents in symmetrical 145 K+ recording solutions at negative patch potentials near the resting membrane potential of LSMCs. Unitary amplitudes calculated over a range of negative patch potentials from −80 mV to −30 mV indicate a single‐channel conductance of ~ 37 pS. Thus, we have tentatively identified the KATP channel in rat LSMCs as a first step toward defining it's regulation by endogenous substances and pharmacological interventions that may alter lymph flow.Support or Funding InformationSupported by T32 GM106999 (BRG) and R21 CA187325‐01A1 (NJR) from the National Institutes of Health.