TY - JOUR

T1 - The contribution of K(+) channels to human thoracic duct contractility

AU - Telinius, Niklas

AU - Kim, Sukhan

AU - Pilegaard, Hans

AU - Pahle, Einar

AU - Nielsen, Jørn

AU - Hjortdal, Vibeke

AU - Aalkjaer, Christian

AU - Boedtkjer, Donna Briggs

PY - 2014/7/1

Y1 - 2014/7/1

N2 - In smooth muscle cells, K(+) permeability is high, and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by smooth muscle cells of lymphatic vessels, and it is likely that K(+) channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct K(+) channels to human lymphatic vessel contractility. Thoracic ducts were harvested from 43 patients and mounted in a wire myograph for isometric force measurements or membrane potential recordings with an intracellular microelectrode. Using K(+) channel blockers and activators, we demonstrate a functional contribution to human lymphatic vessel contractility from all the major classes of K(+) channels [ATP-sensitive K(+) (KATP), Ca(2+)-activated K(+), inward rectifier K(+), and voltage-dependent K(+) channels], and this was confirmed at the mRNA level. Contraction amplitude, frequency, and baseline tension were altered depending on which channel was blocked or activated. Microelectrode impalements of lymphatic vessels determined an average resting membrane potential of -43.1 ± 3.7 mV. We observed that membrane potential changes of <5 mV could have large functional effects with contraction frequencies increasing threefold. In general, KATP channels appeared to be constitutively open since incubation with glibenclamide increased contraction frequency in spontaneously active vessels and depolarized and initiated contractions in previously quiescent vessels. The largest change in membrane voltage was observed with the KATP opener pinacidil, which caused 24 ± 3 mV hyperpolarization. We conclude that K(+) channels are important modulators of human lymphatic contractility.

AB - In smooth muscle cells, K(+) permeability is high, and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by smooth muscle cells of lymphatic vessels, and it is likely that K(+) channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct K(+) channels to human lymphatic vessel contractility. Thoracic ducts were harvested from 43 patients and mounted in a wire myograph for isometric force measurements or membrane potential recordings with an intracellular microelectrode. Using K(+) channel blockers and activators, we demonstrate a functional contribution to human lymphatic vessel contractility from all the major classes of K(+) channels [ATP-sensitive K(+) (KATP), Ca(2+)-activated K(+), inward rectifier K(+), and voltage-dependent K(+) channels], and this was confirmed at the mRNA level. Contraction amplitude, frequency, and baseline tension were altered depending on which channel was blocked or activated. Microelectrode impalements of lymphatic vessels determined an average resting membrane potential of -43.1 ± 3.7 mV. We observed that membrane potential changes of <5 mV could have large functional effects with contraction frequencies increasing threefold. In general, KATP channels appeared to be constitutively open since incubation with glibenclamide increased contraction frequency in spontaneously active vessels and depolarized and initiated contractions in previously quiescent vessels. The largest change in membrane voltage was observed with the KATP opener pinacidil, which caused 24 ± 3 mV hyperpolarization. We conclude that K(+) channels are important modulators of human lymphatic contractility.

KW - Aged

KW - Excitation Contraction Coupling/physiology

KW - Female

KW - Humans

KW - In Vitro Techniques

KW - Ion Channel Gating/physiology

KW - Isometric Contraction/physiology

KW - Male

KW - Muscle, Smooth/physiology

KW - Potassium Channels/physiology

KW - Thoracic Duct/physiology

U2 - 10.1152/ajpheart.00921.2013

DO - 10.1152/ajpheart.00921.2013

M3 - Journal article

C2 - 24778167

VL - 307

SP - H33-43

JO - A J P: Heart and Circulatory Physiology (Online)

JF - A J P: Heart and Circulatory Physiology (Online)

SN - 1522-1539

IS - 1

ER -