Affiliation:
1. From the Department of Medicine, Division of Pulmonary and Critical Care Medicine, and the Department of Physiology, University of Maryland School of Medicine, Baltimore.
Abstract
Abstract
The membrane potential (E
m
) of pulmonary arterial smooth muscle cells (PASMCs) regulates pulmonary arterial tone by controlling voltage-gated Ca
2+
channel activity, which is a major contributor to [Ca
2+
]
i
. The resting membrane is mainly permeable to K
+
; thus, the resting E
m
is controlled by K
+
permeability through sarcolemmal K
+
channels. At least three K
+
currents, voltage-gated K
+
(K
V
) currents, Ca
2+
-activated K
+
(K
Ca
) currents, and ATP-sensitive (K
ATP
) currents, have been identified in PASMCs. In this study, both patch-clamp and quantitative fluorescent microscopy techniques were used to determine which kind(s) of K
+
channels (K
V
, K
Ca
, and/or K
ATP
) is responsible for controlling E
m
and [Ca
2+
]
i
under resting conditions in rat PASMCs. When the bath solution contained 1.8 mmol/L Ca
2+
and the pipette solution included 0.1 mmol/L EGTA, depolarizations (−40 to +80 mV) elicited both K
Ca
and K
V
currents. Removal of extracellular Ca
2+
and increase of intracellular EGTA concentration (to 10 mmol/L) eliminated the Ca
2+
influx–dependent K
Ca
current. 4-Aminopyridine (4-AP, 5 to 10 mmol/L) but not charybdotoxin (ChTX, 10 to 20 nmol/L) significantly reduced K
V
current under these conditions. In current-clamp experiments, 4-AP decreased E
m
(depolarization) and induced Ca
2+
-dependent action potentials; this depolarization increased [Ca
2+
]
i
in intact PASMCs. Neither ChTX nor the specific blocker of K
ATP
channels, glibenclamide (2 to 10 μmol/L), caused membrane depolarization and the increase in [Ca
2+
]
i
. However, pretreatment of PASMCs with ChTX enhanced the 4-AP–induced increase in [Ca
2+
]
i
. These results suggest that the 4-AP–sensitive K
V
currents that are active in the resting state are the major contributors to regulation of E
m
and thus [Ca
2+
]
i
in rat PASMCs.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
290 articles.
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