Altered contractile and ion channel function in rabbit portal vein with
dietary atherosclerosis.
Cox, R. H., and T. N. Tulenko.
Bockus Research Institute, The Graduate Hospital; Department of Physiology,
University of Pennsylvania; and Department of Physiology, Medical College of
Pennsylvania, Philadelphia, PA
APStracts 2:0003H, 1995.
This study was performed to determine the effects of dietary atherosclerosis
on the pharmacology and ion channel properties of smooth muscle in the rabbit
portal vein (PV). New Zealand white rabbits were fed normal rabbit chow +/- 2%
cholesterol for 10 weeks. Contractions to norepinephrine and serotonin were
studied under isometric conditions using longitudinal strips. Single smooth
muscle cells were isolated by collagenase plus elastase treatment, and Ca2+
and K+ currents (ICa and IK) recorded using whole-cell voltage clamp methods.
Cholesterol feeding increased total plasma cholesterol levels from 28.4+/-5.2
to 1387+/-172 mg/dl as well as the cholesterol to phospholipid molar ratio of
the PV from 0.34+/-0.02 to 0.66+/-0.08. Maximal contractile responses to KCl
and norepinephrine (NE) were not significantly different in atherosclerotic PV
but those to serotonin (5HT) were larger only when normalized to the maximum
KCl response. Concentration-active stress curves to NE and 5HT were shifted to
the left in the atherosclerotic PV compared to control. The ED50 for NE and
the threshold concentration of 5HT were significantly smaller in the
atherosclerotic PV. Maximum values of ICa normalized by cell capacitance were
larger in myocytes from atherosclerotic compared to control animals (4.4+/-0.4
vs 3.1+/-0.2 pA/pF, p<0.05). The voltage dependence of activation and
availability of ICa was shifted toward more negative potentials by about
10mV. Whole cell K+ currents were significantly smaller in atherosclerotic
myocytes. At a test voltage of +20mV, IK average 14.9+/-2.8 pA/pF in control
compared to 7.7+/-0.8 pA/pF in atherosclerotic myocytes from a holding
potential of -80mV with [Ca2+]o = 5 mM. The reversal potential for IK
tail currents was significantly less negative in atherosclerotic myocytes (
-70+/-1 vs -64+/-1 mV). These results demonstrate that augmentation of
vascular smooth muscle contractile responses occur at venous as well as
arterial sites in dietary atherosclerosis. Changes in Ca2+ (increased ICa) and
K+ (decreased IK) channels could increase Ca2+ influx, and contribute to the
increased contractile "sensitivity" of vascular smooth muscle in
atherosclerosis.
Received 28 March 1994; accepted in final form 5 January 1995.
APS Manuscript Number H0275-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.