Hyperpolarisation-activated inward current in isolated sheep mesenteric lymphatic smooth muscle.

McCloskey, K. D. and Toland, H. M. and Hollywood, Mark A. and Thornbury, Keith D. and McHale, Noel G. (1999) Hyperpolarisation-activated inward current in isolated sheep mesenteric lymphatic smooth muscle. J Physiol. , 521 (1). pp. 201-211.

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Freshly isolated sheep lymphatic smooth muscle cells were studied using the perforated patch-clamp technique. Hyperpolarisation with constant-current pulses caused a time-dependent rectification evident as a depolarising 'sag' followed by an anode-break overshoot at the end of the pulse. Both sag and overshoot were blocked with 1 mM Cs+. 2. Cells were voltage clamped at -30 mV and stepped to -120 mV in 10 mV steps of 2 s duration. Steps negative to -60 mV evoked a slowly activating, non-inactivating inward current which increased in size and rate of activation with increasing hyperpolarisation. 3. The slowly activating current was reduced in Na+-free bathing solution but enhanced when the extracellular K+ concentration was increased to 60 mM. The current was significantly reduced by 1 mM Cs+ and 1 microM ZD7288 but not by 1.8 mM Ba2+. 4. The steady-state activation curve of the underlying conductance showed a threshold at -50 mV and half-maximal activation at -81 mV. Neither threshold nor half-maximal activation was significantly affected by increasing the external K+ concentration to 60 mM. 5. The frequency of spontaneous contractions and fluid propulsion in isolated cannulated segments of sheep mesenteric lymphatics were decreased by 1 mM Cs+ and by 1 microM ZD7288. 6. We conclude that sheep lymphatics have a hyperpolarisation-activated inward current similar to the If seen in sinoatrial node cells of the heart. Blockade of this current slows spontaneous pumping in intact lymphatic vessels suggesting that it is important in normal pacemaking.

Item Type: Article
Uncontrolled Keywords: Animals; Barium/pharmacology; Cesium/pharmacology; Evoked Potentials/drug effects; Female; Lymphatic System/drug effects; Lymphatic System/metabolism; Lymphatic System/physiology; Male; Membrane Potentials; Mesentery; Muscle Contraction/drug effects; Muscle, Smooth/drug effects; Muscle, Smooth/metabolism; Muscle, Smooth/physiology; Patch-Clamp Techniques; Potassium/pharmacology; Pyrimidines/pharmacology; Sheep; Sodium/pharmacology
Subjects: Science
Research Centres: Smooth Muscle Research Centre
Depositing User: Concepta Woods
Date Deposited: 08 Mar 2012 16:20
Last Modified: 11 Nov 2014 16:10

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