Sympathetic control of intracellular pH in guinea pig ventricular myocytes;
citation_date
1994-12
Description
Catecholamines affect intracellular pH (pHi) by changing the activities of the ion transporters involved in pHi regulation, but the results are confusing and the mechanisms are not clear. This study examined the effects of catecholamines on pHi regulatory systems. In addition, the intracellular mechanisms involved in the catecholamine responses were investigated. Intracellular pHi was measured in adult guinea pig ventricular myocytes with the fluorescent proton indicator, SNARF-1. In the absence of C02/HC0¯3, the ?1-adrenergic agonist, phenylephrine, caused an increase in steady state pHi and enhanced the rate of pHi recovery from acid loading (dpHi/dt). The phorbol ester, PMA and the DAG analog, DiC8 1,2 had a similar effect. PMA effects on pHi were abolished by staurosporine, a protein kinase C (PKC) inhibitor, and the amiloride derivative, EIPA. PMA effects on steady state pHi were not affected by changes in intracellular Ca2+. These results suggest that the ?1-agonist stimulates Na+/H+ exchange and that the effect is mediated by a Ca2+ independent form of PKC. In the absence of C02/HC0¯3, the ?1-agonist, isoproterenol (ISO), caused a fall in steady state pHi that was sensitive to EIPA and Na+o but not Ca2+. The ISO-induced acidosis was slightly decreased by the cAMP-dependent protein kinase inhibitor, HA-1004. ISO caused an attenuation of dpHi/dt; however agents that increase cAMP (forskolin and milrinone) have an opposite effect. ?1-adrenergic stimulation appears to modulate Na+/H+ exchange. ISO-induced inhibition of Na+/H+ exchange is not caused by an increase in Ca2+i. In addition, techniques that increase cAMP or inhibit cAMP-dependent protein kinase activity do not mimic the ISO effect; therefore Na+/H+ exchange inhibition is not mediated through a cAMP-dependent pathway.
Type
text;
citation_publisher
University of Utah
Subject (MESH)
Cell Physiology; Catecholamines;
citation_dissertation_institution
University of Utah;
citation_dissertation_name
PhD;
citation_language
en;
Relation-Is Version Of
Digital reproduction of “Sympathetic control of intracellular pH in guinea pig ventricular myocytes Spencer S. Eccles Health Sciences Library.
