Contribution of voltage-dependent K+ and Ca2+ channels to coronary pressure-flow autoregulation

Zachary C. Berwick, Steven P. Moberly, Meredith C. Kohr, Ethan B. Morrical, Michelle M. Kurian, Gregory M. Dick, Johnathan D. Tune

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The mechanisms responsible for coronary pressure-flow autoregulation, a critical physiologic phenomenon that maintains coronary blood flow relatively constant in the presence of changes in perfusion pressure, remain poorly understood. This investigation tested the hypothesis that voltage-sensitive K+ (KV) and Ca2+ (CaV1.2) channels play a critical role in coronary pressureflow autoregulation in vivo. Experiments were performed in open-chest, anesthetized Ossabaw swine during step changes in coronary perfusion pressure (CPP) from 40 to 140 mmHg before and during inhibition of KV channels with 4-aminopyridine (4AP, 0.3 mM, ic) or CaV1.2 channels with diltiazem (10 lg/min, ic). 4AP significantly decreased vasodilatory responses to H2O2 (0.3-10 lM, ic) and coronary flow at CPPs = 60-140 mmHg. This decrease in coronary flow was associated with diminished ventricular contractile function (dP/dT) and myocardial oxygen consumption. However, the overall sensitivity to changes in CPP from 60 to 100 mmHg (i.e. autoregulatory gain; Gc) was unaltered by 4-AP administration (Gc = 0.46 ± 0.11 control vs. 0.46 ± 0.06 4-AP). In contrast, inhibition of CaV1.2 channels progressively increased coronary blood flow at CPPs>80 mmHg and substantially diminished coronary Gc to -0.20 ± 0.11 (P<0.01), with no effect on contractile function or oxygen consumption. Taken together, these findings demonstrate that (1) KV channels tonically contribute to the control of microvascular resistance over a wide range of CPPs, but do not contribute to coronary responses to changes in pressure; (2) progressive activation of CaV1.2 channels with increases in CPP represents a critical mechanism of coronary pressureflow autoregulation.

Original languageEnglish
Article number0264
JournalBasic Research in Cardiology
Issue number3
StatePublished - May 2012


  • Autoregulation
  • Calcium channel
  • Coronary blood flow
  • Potassium channel
  • Swine


Dive into the research topics of 'Contribution of voltage-dependent K+ and Ca2+ channels to coronary pressure-flow autoregulation'. Together they form a unique fingerprint.

Cite this