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Expression and function of neuronal nicotinic ACh receptors in rat microvascular endothelial cells

¹School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072 Australia; and ²Department of Cell and Molecular Physiological and Pharmacological Sciences, University of Pavia, 27100 Pavia, Italy

Submitted 2 July 2003 ; accepted in final form 22 September 2003

The expression and function of nicotinic ACh receptors (nAChRs) in rat coronary microvascular endothelial cells (CMECs) were examined using RT-PCR and whole cell patch-clamp recording methods. RT-PCR revealed expression of mRNA encoding for the subunits ₂, ₃, ₄, ₅, ₇, ₂, and ₄ but not ₃. Focal application of ACh evoked an inward current in isolated CMECs voltage clamped at negative membrane potentials. The current-voltage relationship of the ACh-induced current exhibited marked inward rectification and a reversal potential (E_rev) close to 0 mV. The cholinergic agonists nicotine, epibatidine, and cytisine activated membrane currents similar to those evoked by ACh. The nicotine-induced current was abolished by the neuronal nAChR antagonist mecamylamine. The direction and magnitude of the shift in E_rev of nicotine-induced current as a function of extracellular Na⁺ concentration indicate that the nAChR channel is cation selective and follows that predicted by the Goldman-Hodgkin-Katz equation assuming K⁺/Na⁺ permeability ratio of 1.11. In fura-2-loaded CMECs, application of ACh, but not of nicotine, elicited a transient increase in intracellular free Ca²⁺ concentration. Taken together, these results demonstrate that neuronal nAChR activation by cholinergic agonists evokes an inward current in CMECs carried primarily by Na⁺, which may contribute to the plasma nicotine-induced changes in microvascular permeability and reactivity induced by elevations in plasma nicotine.

microvascular endothelium; mRNA expression; acetylcholine-evoked current; nicotinic receptor subunits; intracellular calcium

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