Differential Distribution of Electrophysiologically Distinct Myocytes in Conduit and Resistance Arteries Determines Their Response to Nitric Oxide and Hypoxia
| Autor: | Simona Tolarova, Evangelos D. Michelakis, Stephen L. Archer, Edward K Weir, Vaclav Hampl, James M.C. Huang, Helen L. Reeve |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Potassium Channels Vascular smooth muscle Charybdotoxin Physiology In Vitro Techniques Pulmonary Artery Biology Nitric Oxide Muscle Smooth Vascular chemistry.chemical_compound Internal medicine medicine Animals Myocyte Patch clamp 4-Aminopyridine Membrane potential Tetraethylammonium Cell Hypoxia Culture Media Rats Electrophysiology Endocrinology chemistry Vasoconstriction Circulatory system Biophysics Cardiology and Cardiovascular Medicine |
| Zdroj: | Circulation Research. 78:431-442 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Abstract The cellular mechanisms that determine differences in reactivity of arteries of varying size and origin are unknown. We evaluated the hypothesis that there is diversity in the distribution of K + channels between vascular smooth muscle (VSM) cells within a single segment of the pulmonary arteries (PAs) and that there are differences in the prevalence of these cell types between conduit and resistance arteries, which contribute to segmental differences in the vascular response to NO and hypoxia. Three types of VSM cells can be identified in rat PAs on the basis of their whole-cell electrophysiological properties—current density and the pharmacological dissection of whole-cell K + current (I K )—and morphology. Cells are referred to as “K Ca , K DR , or mixed,” acknowledging the type of K + channel that dominates the I K : the Ca 2+ -sensitive (K Ca ) channel, delayed rectifier (K DR ) channel, or a mixture of both. The three cell types were identified by light and electron microscopy. K Ca cells are large and elongated, and they have low current density and currents that are inhibited by tetraethylammonium (5 mmol/L) or charybdotoxin (100 nmol/L). K DR cells are smaller, with a perinuclear bulge, but have high current density and currents that are inhibited by 4-aminopyridine (5 mmol/L). Conduit arteries contain significant numbers of K Ca cells, whereas resistance arteries have a majority of K DR cells and few K Ca cells. NO rapidly and reversibly increases I K and hyperpolarizes K Ca cells because of an increase in open probability of a 170-pS K Ca channel. Hypoxia depolarizes K DR cells by rapidly and reversibly inhibiting one or more of the tonically active K DR channels (including a 37-pS channel) that control resting membrane potential. The effects of both hypoxia and NO on K + channels are evident at negative membrane potentials, supporting their physiological relevance. The functional correlate of this electrophysiological diversity is that K DR -enriched resistance vessels constrict to hypoxia, whereas conduit arteries have a biphasic response predominated by relaxation. Although effective in both segments, NO relaxes conduit more than resistance rings, in both cases by a cGMP-dependent mechanism. We conclude that regional electrophysiological diversity among smooth muscle cells is a major determinant of segmental differences in vascular reactivity. |
| Databáze: | OpenAIRE |
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