α 1 -Adrenergic Stimulation of Sarcolemmal Na + -H + Exchanger Activity in Rat Ventricular Myocytes

Abstract

Abstract —α 1 -Adrenoceptor (α 1 -AR) stimulation increases sarcolemmal Na + -H + exchanger (NHE) activity. The present study was designed to determine the role(s) of α 1 -AR subtype(s) in mediating this response. As an index of NHE activity, acid efflux rates ( J H s) were determined in single rat ventricular myocytes loaded with the pH-sensitive fluoroprobe carboxy-seminaphthorhodafluor-1 after 2 consecutive intracellular acid pulses in bicarbonate-free medium. J H at pH i 6.90 did not change significantly during the second pulse relative to the first in control cells but increased in a dose-dependent manner when the second pulse occurred in the presence of phenylephrine (nonselective α 1 -AR agonist) or A61603 (α 1A -AR–selective agonist), with EC 50 values of 1.24 μmol/L and 3.6 nmol/L, respectively (both agonists given together with 1 μmol/L atenolol). Stimulation of NHE activity by 10 μmol/L phenylephrine was inhibited in a dose-dependent manner by the competitive antagonists prazosin, WB4101, and 5-methylurapidil, with IC 50 values of 12, 32, and 149 nmol/L, respectively. Analyses of the relative EC 50 and IC 50 values obtained (and K i values estimated from the antagonist IC 50 s) in relation to the relative potencies of these agents at native rat α 1 -AR subtypes and their relative affinities for recombinant rat α 1 -ARs suggest that α 1 -adrenergic stimulation of sarcolemmal NHE activity is likely to be mediated selectively by the α 1A -AR.