Table Of ContentIon Flux in Pulmonary
Vascular Control
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Series A: Life Sciences
Ion Flux in Pulmonary
Vascular Control
Edited by
E. Kenneth Weir
Veterans Administration Medical Center
Minneapolis, Minnesota
Joseph R. Hume
University of Nevada
Reno, Nevada
and
John T. Reeves
University of Colorado
Denver, Colorado
Springer Science+Business Media, LLC
Proceedings of a NATO Advanced Research Workshop:
The Sixth Grover Conference on the Pulmonary Circulation,
held October 15-18, 1992,
in Sedalia, Colorado
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Library of Congress Catalog1ng-1n-Pub1icatIo n Data
Ion flu x i n pulmonary vascula r contro l / edite d by E. Kenneth Weir,
Joseph R. Hume, and John T. Reeves.
p. cm . — (NATO ASI series . Serie s A. Lif e science s v.
;
251)
"Proceedings of a NATO advanced researc h workshop, the Sixth
Grover Conference on the Pulmonary Circulation , held October 15-18 ,
1992, i n Sedalia, Colorado"—T.p . verso .
"Published i n cooperation wit h NATO Scientifi c Affair s Division. "
Includes bibliographica l reference s an d index .
ISBN 978-1-4613-6016-2
1. Pulmonary circulation—Regulation—Congresses . 2 . Pulmonary
endothelium—Congresses. 3 . Ion channels—Congresses. 4 . Vascular
smooth muscle—Congresses. 5 . Vascular endothelium—Congresses .
6. Pulmonary hypertension—Congresses . I . Weir, E. Kenneth.
II. Hume, Joseph Randy, 1947- . III . Reeves. John T. IV . North
Atlanti c Treat y Organization . Scientifi c Affair s Division .
V. Grover Conference on the Pulmonary Circulatio n (6t h : 1992 :
Sedalia. Colo. ) VI . Series.
[DNLM: 1. Ion Channels—congresses. 2 . Pulmonary Clrculation -
-physiology—congresses . 3 . Endothelium, Vascular—physiology -
-congresses. W F 600 164 1992]
QP107.156 199 3
612.2—dc20
DNLM/DCL
for Librar y of Congress 93-562 8
CIP
ISBN 978-1-4613-6016-2 ISBN 978-1-4615-2397-0 (eBook)
DOI 10.1007/978-1-4615-2397-0
©1993 Springer Science+Business Media New York
Originally published by Plenum Press.New York in 1993
Softcover reprint of the hardcover 1st edition 1993
All rights reserved
No part of this book may be reproduced, stored in retrieval system, or transmitted in any
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otherwise, without written permission from the Publisher
PREFACE
Ions can pass through a single membrane channel at a rate of 106
ions/second. Over the last decade the ability to measure ion flux so
precisely and to document the opening and closing of individual ion
channels has provided a powerful tool to those working on smooth
muscle physiology and vascular reactivity. The use of potassium channel
blockers by Tom Lloyd in the 1960s and calcium channel blockers by
Ivan McMurtry in the 1970s indicated the importance of ion flux in
regulating pulmonary vascular tone. Recent advances in technology.
principally the patch-clamp technique and fluorescent ion-sensitive dyes.
now permit a more detailed description of physiologic mechanisms.
This volume arises from the Sixth Grover Conference on the
Pulmonary Circulation. a NATO Advanced Research Workshop. held in
Colorado in October 1992. A group of international sCientists who are
leaders in the field of ion flux focused their attention on the problems of
the pulmonary vasculature. The chapters in this book describe the
present state of knowledge of the movement and storage of ions in
vascular endothelial and smooth muscle cells. Those who are not
familiar with the techniques of patch clamping and calcium imaging will
find an introduction to these methods in the chapters by Leblanc and
Wan and Archer et al.
The role of potassium channels in oxygen sensing illustrates the
rapid progress which the study of ion currents has made possible.
Several chapters describe the concept that hypoxic inhibition of one or
more potassium channels may lead to membrane depolarization and
signal a fall in oxygen tension. The possibility that oxygen tension alters
gating of the potaSSium channels through changes in redox status is
discussed by Post et al.
The endothelium modulates pulmonary and systemic vascular
reactivity and permeability. Five chapters examine the function of ion
channels and ion flux in endothelial cells. Measurement of intracellular
calCium and patch-clamp techniques have provided new insights into
endothelial control mechanisms. such as the action of endothelium
dependent vasodilators. These dilators increase cytosolic calcium by
inducing both calcium entry through receptor-operated channels and
calcium release from intracellular stores. Calcium-dependent potassium
channels are then activated. leading to hyperpolarization which generates
the electrochemical gradient for further calCium entry. Differences in the
handling of ions between cultured and freshly dispersed endothelial cells
remain to be resolved.
This NATO workshop provided the opportunity for the interchange
of an immense amount of information. The book is the distillation of that
information. written immediately after the conference. with the advantage
v
of that intense period of discussion. The organizing committee is grateful
to the sponsors of the meeting. especially the Scientific Affairs Division of
NATO. the National Heart. Lung and Blood Institute of the National
Institutes of Health. Axon Instruments. Inc .. Burroughs Wellcome
Company. Marion Merrell Dow Inc .. Merck Sharp & Dohme. Pfizer
Laboratories. the Upjohn Company. and the Pulmonary Circulation
Foundation.
E. Kenneth Weir
Joseph R. Hume
John T. Reeves
vi
CONTENTS
Introduction
Pulmonary Hypertension: From Phenomenology to a Molecular. . . . . . 1
Understanding of Disease Mechanisms
N.F. Voelkel
The Electrophysiology of Smooth Muscle Cells and Techniques for. . . 15
Studying Ion Channels
N. Leblanc and X. Wan
CALCIUM CONTROL IN SMOOTH MUSCLE
CalCium Channels in Arterial Smooth Muscle Cells. . . . . . . . . . . . . . . 41
J .M. Quayle and M. T. Nelson
Interactions of Intracellular Ca2+ Pools in Vascular Smooth Muscle. . 49
C. van Breemen and Q. Chen
Na-Ca Exchange in Isolated Coronary Myocytes: A Study Combining. . 57
Voltage clamp and Ca2+ Fluorometry
G. Isenberg and V. Ganitkevich
Role of CalCium ATPases in Pulmonary Vascular Reactivity. . . . . . . . . 67
I.S. Farrukh and J.R. Michael
Fast Na+ Current and Ca2+ Currents in Smooth Muscles. . . . . . . . . . 77
N. Sperelakis, Z. Xiong, Y. Inoue, Y. Ohya, K. Shimamura,
D. Bielefeld and J. Lorenz
Influence of Physical and Environmental Factors on Ion Channels. . .. 105
in Arterial Muscle
D.R. Harder, D. Gebremedhin and R.J. Roman
vii
POTASSIUM CHANNELS IN VASCULAR SMOOTH MUSCLE
Potassium Channels Activated by Calcium Released from the . . . . . . III
Sarcoplasmic Reticulum in Vascular Smooth Muscles
K. Kitamura. H. Kuriyama and H. Nabata
ATP-Sensitive Potassium Channels in the Pulmonary Vasculature. .. 129
L.H. Clapp and A.M. Gurney
Electrophysiological Actions of Extracellular ATP Application. . . . . .. 141
C.D. Benham
An ATP-Activated Potassium Channel in Smooth Muscle Cells from. . 149
the Pulmonary Artery
S. Albarwani and P. Nye
The Effect of Prostacyclin Analogs on Vascular K Channels. . . . . . . . 159
G. Siegel. M. Bostanjoglo. K. Riickborn. F. Schnalke.
J. Mironneau and G. Stock
POTASSIUM CHANNELS AND OXYGEN SENSING
Potassium Channel Modulated by Hypoxia and the Redox Status in. . 177
Glomus Cells of the Carotid Body
A.R. Benot. M.D. Ganfornina and J. LOpez-Barneo
Redox Regulation of Potassium Channels and Hypoxic Pulmonary. .. 189
Vasoconstriction
J.M. Post. E.K. Weir. S.L. Archer and J.R. Hume
The Sodium Gradient. Potassium Channels. and Regulation of. . . . .. 205
Calcium in Pulmonary and Mesenteric Arterial Smooth
Muscle: Effects of Hypoxia
X.-J. Yuan. C.G. Salvaterra. M.L. Tod. M. Juhaszova.
W.F. Goldman. L.J. Rubin and M.P. Blaustein
ION FLUX IN VASCULAR ENDOTHELIAL CELLS
The Importance of Calcium in the Regulation of EDRF Synthesis in .. 223
the Pulmonary Vasculature
S.L. Archer. V. Hampl, J. Huang and N. Cowan
viii
The Role of Ion Channels in Vascular Endothelium. . . . . . . . . . . . . . 247
A Liickhoff
Calcium Signalling in Vascular Endothelial Cells: Calcium Entry. . . . 259
and Release
D.J. Adams. J. Rusko and G. Van Slooten
Mechanosensitive Ion Channels in Vascular Endothelial Cells. . . . .. 277
T.R. Elam and J.B. Lansman
Membrane Hyperpolarization as a Mechanism for Endothelium- . . . . 287
Dependent Vasodilation
J .E. Brayden
The Interaction between Flow-Induced Vasoconstriction and. . . . . .. 297
Vasodilation: A Mechanism for Setting the Level of Vascular
Tone
J.A Bevan
THERAPY OF PULMONARY HYPERTENSION
Correlation of Acute Prostacyclin Response in Primary. . . . . . . . . . . 317
(Unexplained) Pulmonary Hypertension with Efficacy of
Treatment with Calcium Channel Blockers and Survival
B.M. Groves. D.B. Badesch. D. Turkevich. R.V. Ditchey.
K. Donnellan. K. Wynne. AD. Robertson. W.A Long.
N. Voelkel and J.T. Reeves
Role of Endothelium-Derived Nitric Oxide in Perinatal Pulmonary. . . 331
Vasoregulation
S.H. Abman. D.N. Cornfield and J.P. Kinsella
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
ix
PULMONARY HYPERTENSION: FROM PHENOMENOLOGY TO A
MOLECULAR UNDERSTANDING OF DISEASE MECHANISMS
Norbert F. Voelkel
Pulmonary and Critical Care Division
University of Colorado Health Sciences Center
4200 E. 9th Ave.
C-272
Denver, Colorado 80262
Science is the art of shaping questions and identifying the underlying
assumptions. Nature has' no secrets. The obstacles to furthering
knowledge lie in the formulation of new, probing questions. Artful
questions often require new technology from unrelated disciplines. *
INTRODUCTION
The pulmonary circulation is anatomically defined as the vasculature between the
right ventricle and the left atrium; under normal conditions this circulation accommodates
the entire cardiac output, yet it is a low pressure, - low resistance system. Leaving the
right ventricle, the blood enters the central conduit arteries that have Windkessel -
function, then enters rapidly branching muscular arteries, and finally the precapillary
resistance vessels. Whereas flow and pressure have been studied with great intensity, cell
cell interactions in the lung capillaries are only recently gaining attention (1-3). Flow
passive opening of reserve capillaries is a major regulatory factor in the control of the lung
circulation and there is the general consensus that the lung circulation does not possess a
significant myogenic tone (4). The lung vessels are innervated by both sympathetic and
parasympathetic fibers, and it is evident that small changes in the pulmonary venous tone
can have devastating effects on capillary fluid filtration - leading to edema formation (5).
Large amounts of new information regarding the control of lung vessels under normal
Tribute to Robert F. Grover
.j<
Ion Flux in Pulmonary Vascular Control, Edited by
E.K. Weir et al., Plenum Press, New York, 1993
