Affiliation:
1. From the Research Center, Montreal Heart Institute, Montréal, Québec, Canada.
Abstract
Abstract
—Large-conductance Ca
2+
-dependent K
+
channels (K
Ca
), which are abundant on the sarcolemma of vascular myocytes, provide negative feedback via membrane hyperpolarization that limits Ca
2+
entry through L-type Ca
2+
channels (
I
CaL
). We hypothesize that local accumulation of subsarcolemmal Ca
2+
during
I
CaL
openings amplifies this feedback. Our goal was to demonstrate that Ca
2+
entry through voltage-gated
I
CaL
channels can stimulate adjacent K
Ca
channels by a localized interaction in enzymatically isolated rabbit coronary arterial myocytes voltage clamped in whole-cell or in cell-attached patch clamp mode. During slow-voltage-ramp protocols, we identified an outward K
Ca
current that is activated by a subsarcolemmal Ca
2+
pool dissociated from bulk cytosolic Ca
2+
pool (measured with indo 1) and is dependent on L-type Ca
2+
channel activity. Transient activation of unitary K
Ca
channels in cell-attached patches could be detected during long step depolarizations to +40 mV (holding potential, −40 mV; 219 pS in near-symmetrical K
+
). This local interaction between the channels required the presence of Ca
2+
in the pipette solution, was enhanced by the
I
CaL
agonist Bay K 8644, and persisted after impairment of the sarcoplasmic reticulum by incubation with 10 μmol/L ryanodine and 30 μmol/L cyclopiazonic acid for at least 60 minutes. Furthermore, we provide the first direct evidence of simultaneous openings of single K
Ca
(67 pS) and
I
CaL
(3.9 pS) channels in near-physiological conditions, near resting membrane potential. Our data imply a novel sensitive mechanism for regulating resting membrane potential and tone in vascular smooth muscle.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
50 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献