Faculty Collaboration Database

Intracellular acidosis differentially regulates KV channels in coronary and pulmonary vascular muscle. Am J Physiol 1998 Oct;275(4):H1351-9

Date

09/24/1998

Pubmed ID

9746485

DOI

10.1152/ajpheart.1998.275.4.H1351

Scopus ID

2-s2.0-33750889550 (requires institutional sign-in at Scopus site)   64 Citations

Abstract

Decreases in intracellular pH (pHi) potently dilate coronary resistance arteries but constrict small pulmonary arteries. To define the ionic mechanisms of these responses, this study investigated whether acute decreases in pHi differentially regulate K+ currents in single vascular smooth muscle (VSM) cells isolated from rat coronary and pulmonary resistance arteries. In patch-clamp studies, whole cell K+ currents were elicited by 10-mV depolarizing steps between -60 and 0 mV in VSM cells obtained from 50- to 150-micrometers-OD arterial branches, and pHi was lowered by altering the NH4Cl gradient across the cell membrane. Progressively lowering pHi from calculated values of 7.0 to 6.7 and 6.4 increased the peak amplitude of K+ current in coronary VSM cells by 15 +/- 5 and 23 +/- 3% but reduced K+ current in pulmonary VSM cells by 18 +/- 3 and 21 +/- 3%, respectively. These changes were reversed by returning cells to the control pHi of 7.0 and were eliminated by dialyzing cells with pipette solution containing 50 mmol/l HEPES to buffer NH4Cl-induced changes in pHi. Pharmacological block of ATP-sensitive K+ channels and Ca2+-activated K+ channels by 1 micromol/l glibenclamide and 100 nmol/l iberiotoxin, respectively, did not prevent changes in K+ current levels induced by acidotic pHi. However, block of voltage-gated K+ channels by 3 mmol/l 4-aminopyridine abolished acidosis-induced changes in K+ current amplitudes in both VSM cell types. Interestingly, alpha-dendrotoxin (100 nmol/l), which blocks only select subtypes of voltage-gated K+ channels, abolished the acidosis-induced decrease in K+ current in pulmonary VSM cells but did not affect the acidosis-induced increase in K+ current observed in coronary VSM cells. These findings suggest that opposing, tissue-specific effects of pHi on distinct subtypes of voltage-gated K+ channels in coronary and pulmonary VSM membranes may differentially regulate vascular reactivity in these two circulations under conditions of acidotic stress.

Author List

Berger MG, Vandier C, Bonnet P, Jackson WF, Rusch NJ

Author

Marcie G. Berger MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

4-Aminopyridine
Acidosis
Ammonium Chloride
Animals
Cell Membrane
Coronary Vessels
Elapid Venoms
Glyburide
Hydrogen-Ion Concentration
In Vitro Techniques
Membrane Potentials
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Peptides
Potassium Channel Blockers
Potassium Channels
Pulmonary Artery
Rats
Rats, Sprague-Dawley