Changes in stretch-induced tone induced by intracellular acidosis in rabbit basilar artery: effects on BKCa channel activity.
It is known that myogenic reactivity is a fundamental determinant of the relative constancy of blood flow through the cerebral artery. It is also known that acute alteration of pH significantly affects the cerebral circulation and, therefore, we investigated the effect of mechanism of action of intracellular acidosis on myogenic tone in rabbit basilar artery. Myogenic tone was developed by imposed stretch of basilar artery and intracellular acidosis induced by the bath application of 20 mmol/L sodium acetate. Sodium acetate caused a biphasic increase in myogenic tone. The initial component reached a peak quickly and then fell slowly to a lower steady-state significantly above basal tone. The sodium acetate-induced increase in myogenic tone was completely inhibited by elimination of external Ca2+, or treatment of nifedipine, but not with gadolinium or NPPB. TEA (5 mmol/L) and iberiotoxin (100 nmol/L) inhibited the sodium acetate-induced increase in myogenic tone. In inside-out patch-clamp recordings, decreasing pH of the mock intracellular solution from 7.4 to 6.9 markedly inhibited BKCa currents. Several inhibitors involved in Ca2+ sensitization pathways, 10(-6) mol/L Y-27632, 5 x 10(-7) mol/L calphostin C and 10(-5) mol/L PD98059 had no effect on the sodium acetate-induced increase in myogenic tone. These results suggest that intracellular acidosis increases stretch-induced myogenic tone in rabbit basilar artery. Furthermore, voltage-dependent Ca2+ influx plays a key role in intracellular acidosis-induced increase in myogenic tone and may be mediated, at least in part, by inhibition of BKCa.
Cho
Young-Eun
YE
BK 21 Project for Medical Sciences, College of Medicine Yonsei University, Seoul, 120-752, South Korea.
Ahn
Duck-Sun
DS
Kim
Young-Hwan
YH
Taggart
Michael J
MJ
Lee
Young-Ho
YH
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D009129:Muscle Tonus / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D013757:Tetraethylammonium Compounds; C064719:iberiotoxin; D009543:Nifedipine; D002118:Calcium