α1-adrenergic stimulation of sarcolemmal Na+-H+ exchanger activity in rat ventricular myocytes -: Evidence for selective mediation by the α1A-adrenoceptor subtype

alpha(1)-Adrenoceptor (alpha(1)-AR) stimulation increases sarcolemmal Na+-H+ exchanger (NHE) activity. The present study was designed to determine the role(s) of alpha(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 alpha(1)-AR agonist) or A61603 (alpha(1A)-AR-selective agonist), with EC50 values of 1.24 mu mol/L and 3.6 nmol/L, respectively (both agonists given together with 1 mu mol/L atenolol). Stimulation of NHE activity by 10 mu mol/L phenylephrine was inhibited in a dose-dependent manner by the competitive antagonists prazosin, WB4101, and 5-methylurapidil, with IC50 values of 12, 32, and 149 nmol/L, respectively. Analyses of the relative ECS, and ICS, 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 alpha(1)-AR subtypes and their relative affinities for recombinant rat alpha(1)-ARs suggest that alpha(1)-adrenergic stimulation of sarcolemmal NHE activity is likely to be mediated selectively by the alpha(1A)-AR.