Abstract
cAMP-dependent phosphorylation clearly increases current through cardiac L-type Ca channels, but the molecular manifestation of this effect remains controversial. Previous work implicates either an increase in the number of functional channels or graded changes in the gating of individual channels. We now find that single cardiac Ca channels display three patterns of activity ("modes") and that isoproterenol or 8-bromoadenosine 3',5'-cyclic monophosphate redistributes the relative proportions of modes such that the two most active (mode 1, bursts of brief openings; mode 2, very long-lasting openings) are favored (P less than 0.05; n = 7). Conversely, a pattern of sparse brief openings (mode 0a) is selectively inhibited (P less than 0.01). Despite differences in the relative frequencies of the various modes before and during drug exposure, the gating within each mode is not detectably changed. We conclude that potentiation of highly active modes of Ca channel gating underlies the enhancement of calcium influx by beta-adrenergic stimulation.
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- Armstrong D., Eckert R. Voltage-activated calcium channels that must be phosphorylated to respond to membrane depolarization. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2518–2522. doi: 10.1073/pnas.84.8.2518. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bean B. P., Nowycky M. C., Tsien R. W. Beta-adrenergic modulation of calcium channels in frog ventricular heart cells. 1984 Jan 26-Feb 1Nature. 307(5949):371–375. doi: 10.1038/307371a0. [DOI] [PubMed] [Google Scholar]
- Blatz A. L., Magleby K. L. Correcting single channel data for missed events. Biophys J. 1986 May;49(5):967–980. doi: 10.1016/S0006-3495(86)83725-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brum G., Osterrieder W., Trautwein W. Beta-adrenergic increase in the calcium conductance of cardiac myocytes studied with the patch clamp. Pflugers Arch. 1984 Jun;401(2):111–118. doi: 10.1007/BF00583870. [DOI] [PubMed] [Google Scholar]
- Catterall W. A. Structure and function of voltage-sensitive ion channels. Science. 1988 Oct 7;242(4875):50–61. doi: 10.1126/science.2459775. [DOI] [PubMed] [Google Scholar]
- Cavalié A., Pelzer D., Trautwein W. Fast and slow gating behaviour of single calcium channels in cardiac cells. Relation to activation and inactivation of calcium-channel current. Pflugers Arch. 1986 Mar;406(3):241–258. doi: 10.1007/BF00640910. [DOI] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
- Horn R., Vandenberg C. A., Lange K. Statistical analysis of single sodium channels. Effects of N-bromoacetamide. Biophys J. 1984 Jan;45(1):323–335. doi: 10.1016/S0006-3495(84)84158-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kokubun S., Reuter H. Dihydropyridine derivatives prolong the open state of Ca channels in cultured cardiac cells. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4824–4827. doi: 10.1073/pnas.81.15.4824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lacerda A. E., Brown A. M. Nonmodal gating of cardiac calcium channels as revealed by dihydropyridines. J Gen Physiol. 1989 Jun;93(6):1243–1273. doi: 10.1085/jgp.93.6.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mikami A., Imoto K., Tanabe T., Niidome T., Mori Y., Takeshima H., Narumiya S., Numa S. Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel. Nature. 1989 Jul 20;340(6230):230–233. doi: 10.1038/340230a0. [DOI] [PubMed] [Google Scholar]
- Niedergerke R., Page S. Analysis of catecholamine effects in single atrial trabeculae of the frog heart. Proc R Soc Lond B Biol Sci. 1977 Jun 15;197(1128):333–362. doi: 10.1098/rspb.1977.0074. [DOI] [PubMed] [Google Scholar]
- Ochi R., Hino N., Okuyama H. Beta-adrenergic modulation of the slow gating process of cardiac calcium channels. Jpn Heart J. 1986 Nov;27 (Suppl 1):51–55. [PubMed] [Google Scholar]
- Rane S. G., Holz G. G., 4th, Dunlap K. Dihydropyridine inhibition of neuronal calcium current and substance P release. Pflugers Arch. 1987 Aug;409(4-5):361–366. doi: 10.1007/BF00583789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
- Reuter H., Scholz H. The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol. 1977 Jan;264(1):49–62. doi: 10.1113/jphysiol.1977.sp011657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sachs F., Neil J., Barkakati N. The automated analysis of data from single ionic channels. Pflugers Arch. 1982 Dec;395(4):331–340. doi: 10.1007/BF00580798. [DOI] [PubMed] [Google Scholar]
- Slish D. F., Engle D. B., Varadi G., Lotan I., Singer D., Dascal N., Schwartz A. Evidence for the existence of a cardiac specific isoform of the alpha 1 subunit of the voltage dependent calcium channel. FEBS Lett. 1989 Jul 3;250(2):509–514. doi: 10.1016/0014-5793(89)80786-0. [DOI] [PubMed] [Google Scholar]
- Tanabe T., Beam K. G., Powell J. A., Numa S. Restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA. Nature. 1988 Nov 10;336(6195):134–139. doi: 10.1038/336134a0. [DOI] [PubMed] [Google Scholar]
- Tsien R. W., Bean B. P., Hess P., Lansman J. B., Nilius B., Nowycky M. C. Mechanisms of calcium channel modulation by beta-adrenergic agents and dihydropyridine calcium agonists. J Mol Cell Cardiol. 1986 Jul;18(7):691–710. doi: 10.1016/s0022-2828(86)80941-5. [DOI] [PubMed] [Google Scholar]
- Yatani A., Brown A. M. Rapid beta-adrenergic modulation of cardiac calcium channel currents by a fast G protein pathway. Science. 1989 Jul 7;245(4913):71–74. doi: 10.1126/science.2544999. [DOI] [PubMed] [Google Scholar]
- Yatani A., Codina J., Imoto Y., Reeves J. P., Birnbaumer L., Brown A. M. A G protein directly regulates mammalian cardiac calcium channels. Science. 1987 Nov 27;238(4831):1288–1292. doi: 10.1126/science.2446390. [DOI] [PubMed] [Google Scholar]
- Yue D. T., Marban E. A novel cardiac potassium channel that is active and conductive at depolarized potentials. Pflugers Arch. 1988 Dec;413(2):127–133. doi: 10.1007/BF00582522. [DOI] [PubMed] [Google Scholar]