| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
1. The ATP-regulated potassium channel (K+ATP) was investigated with respect to modulation by intracellular pH (pHi) by using the inside-out membrane patch clamp technique in ventricular cells isolated from the heart of the guinea-pig. Channels which had been closed by internal ATP (0.3-3 mM) were dose-dependently activated by decreasing the pHi over the range of pH 7.6-6.0. However, the channel was conversely inhibited when the pHi was further decreased below 6.0. Inwardly rectifying K+ channels were also decreased in activity when pHi fell from 7.2 to 6.0. 2. The channel activation was also observed with constant concentration of free Ca2+ (1 nM) and Mg2+ (1 mM) in the bathing solution, suggesting that a change in divalent cation concentration is not involved in channel modulation by pHi. 3. When the dose-response relations of the channel activity for ATP concentrations at different pHi were examined, the channel activity obtained at 1 microM ATP was increased by decreasing pH from 7.2 to 6.4. The half-maximal inhibition for ATP concentration at pH 7.2 and 6.4 was 20 and 40 microM, respectively, and the Hill coefficient was 2.5 in both curves. 4. In the absence of ATP, internal H+ was able to reactivate run-down channels but it had less effect on the channel as long as the activity was maintained at a higher level. The increase in the channel activity by H+ was facilitated with a proceeding of the run-down. However, after the channel was completely inactivated by a long exposure of the membrane patch to ATP-free solution, a reduction of pH could not activate the channel. 5. The decrease of pH from 7.2 to 6.4 reduced single channel conductance from 89.0 to 77.7 pS in the absence of Mg2+, whereas it reduced the conductance only at the negative membrane potentials in the presence of 2 mM Mg2+. 6. Mean open and closed times within the burst-like openings of the channel remained unaffected during the change in pHi. 7. We conclude that the cardiac K+ATP channel is modulated by a change in the intracellular pH. The channel modulation consisted of the increase in the channel activity and a decrease in the permeability. The former effect was due to the decrease in the sensitivity of the channel to ATP and the reactivation of the channel which is during the process of run-down in activity.
This article has been cited by other articles:
|
|
 |
|
  B. Ng, Y. Kang, H. Xie, H. Sun, and H. Y. Gaisano Syntaxin-1A inhibition of P-1075, cromakalim, and diazoxide actions on mouse cardiac ATP-sensitive potassium channel Cardiovasc Res, August 28, 2008; (2008) cvn210v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Hughes and A. Swaminathan Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH Am J Physiol Cell Physiol, February 1, 2008; 294(2): C423 - C431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lu, D. Ye, X. Wang, J. M. Seubert, J. P. Graves, J. A. Bradbury, D. C. Zeldin, and H.-C. Lee Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms J. Physiol., September 1, 2006; 575(2): 627 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kang, B. Ng, Y.-M. Leung, Y. He, H. Xie, D. Lodwick, R. I. Norman, A. Tinker, R. G. Tsushima, and H. Y. Gaisano Syntaxin-1A Actions on Sulfonylurea Receptor 2A Can Block Acidic pH-induced Cardiac KATP Channel Activation J. Biol. Chem., July 14, 2006; 281(28): 19019 - 19028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, Y. Shi, X. Wang, W. Shi, and C. Jiang Single Nucleotide Polymorphisms in KATP Channels: Muscular Impact on Type 2 Diabetes Diabetes, May 1, 2005; 54(5): 1592 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, J. Wu, L. Li, F. Chen, R. Wang, and C. Jiang Hypercapnic Acidosis Activates KATP Channels in Vascular Smooth Muscles Circ. Res., June 13, 2003; 92(11): 1225 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, J. Wu, N. Cui, L. Abdulkadir, R. Wang, J. Mao, L. R. Giwa, S. Chanchevalap, and C. Jiang Distinct Histidine Residues Control the Acid-induced Activation and Inhibition of the Cloned KATP Channel J. Biol. Chem., October 12, 2001; 276(42): 38690 - 38696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Reffelmann, E. C. Skobel, H. Kammermeier, P. Hanrath, and E. R. Schwarz Activation of ATP-Sensitive Potassium Channels in Hypoxic Cardiac Failure Is not Mediated by Adenosine-1 Receptors in the Isolated Rat Heart Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2001; 6(2): 189 - 200. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. McNicholas, G. G. MacGregor, L. D. Islas, Y. Yang, S. C. Hebert, and G. Giebisch pH-dependent modulation of the cloned renal K+ channel, ROMK Am J Physiol Renal Physiol, December 1, 1998; 275(6): F972 - F981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. L. Bethell, J. I. Vandenberg, G. A. Smith, and A. A. Grace Changes in ventricular repolarization during acidosis and low-flow ischemia Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H551 - H561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yokoshiki, M. Sunagawa, T. Seki, and N. Sperelakis ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells Am J Physiol Cell Physiol, January 1, 1998; 274(1): C25 - C37. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shigematsu and M. Arita Anoxia-induced activation of ATP-sensitive K+ channels in guinea pig ventricular cells and its modulation by glycolysis Cardiovasc Res, August 1, 1997; 35(2): 273 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shigematsu, T. Sato, T. Abe, T. Saikawa, T. Sakata, and M. Arita Pharmacological Evidence for the Persistent Activation of ATP-Sensitive K+ Channels in Early Phase of Reperfusion and Its Protective Role Against Myocardial Stunning Circulation, October 15, 1995; 92(8): 2266 - 2275. [Abstract] [Full Text]
|
|
|
|
|
|
H. Xu, N. Cui, Z. Yang, J. Wu, L. R. Giwa, L. Abdulkadir, P. Sharma, and C. Jiang Direct Activation of Cloned KATP Channels by Intracellular Acidosis J. Biol. Chem., April 13, 2001; 276(16): 12898 - 12902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Piao, N. Cui, H. Xu, J. Mao, A. Rojas, R. Wang, L. Abdulkadir, L. Li, J. Wu, and C. Jiang Requirement of Multiple Protein Domains and Residues for Gating KATP Channels by Intracellular pH J. Biol. Chem., September 21, 2001; 276(39): 36673 - 36680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakazaki, M. Kakei, H. Ishihara, N. Koriyama, H. Hashiguchi, K. Aso, M. Fukudome, Y. Oka, T. Yada, and C. Tei Association of upregulated activity of KATP channels with impaired insulin secretion in UCP1-expressing insulinoma cells J. Physiol., May 1, 2002; 540(3): 781 - 789. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
