Alpha 1-adrenergic stimulation exerts net effects on contraction, cytosolic Ca2+, and pH through opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways in rat cardiac myocytes.
Alpha 1-adrenergic stimulation exerts opposing effects on contraction, calcium handling, and pH in rat cardiac myocytes through distinct receptor subtype signaling pathways.
We examined the effect of alpha 1-adrenergic receptor (AR) subtypes on contraction, cytosolic Ca2+ concentration (Ca2+i), and cytosolic pH (pHi) of rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH indicator carboxyseminaphthorhodafluor-1. Nonselective alpha 1-AR stimulation was effected with phenylephrine plus nadolol. alpha 1-AR subtype stimulation was achieved with alpha 1-AR and chloroethylclonidine (CEC) or with alpha 1-AR and WB-4101. Cells were in bicarbonate buffer with 0.5 mM Ca2+ and were electrically stimulated at 0.5 Hz. Results show that 1) nonselective alpha 1-AR stimulation increased twitch and Ca2+i transient amplitudes, myofilament response to Ca2+, and pHi; 2) alpha 1-AR plus CEC increased twitch and Ca2+i transient amplitudes and also enhanced myofilament response to Ca2+ via cytosolic alkalinization; 3) alpha 1-AR plus WB-4101 decreased twitch and Ca2+i transient amplitudes and also pHi; and 4) cytosolic acidification due to alpha 1-AR plus WB-4101 was abolished by protein kinase C inhibition (staurosporine pretreatment) or downregulation (prolonged exposure to phorbol esters). In summary, the net effects of alpha 1-adrenergic stimulation on contraction, Ca2+i, and pHi are due to opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways.
Gambassi et al. (1998) studied Rat ventricular myocytes. Alpha 1-AR subtype stimulation (phenylephrine plus nadolol, CEC, or WB-4101) was evaluated on Contraction, cytosolic Ca2+ concentration ([Ca2+]i), and cytosolic pH (pHi). Alpha 1-adrenergic stimulation exerts net effects on contraction, cytosolic Ca2+, and pH through opposing WB-4101- and CEC-sensitive alpha 1-AR subtype signaling pathways in rat cardiac myocytes.