Characterization of a nicotinamide-adenine dinucleotide-dependent cation channel in the CRI-G1 rat insulinoma cell line

被引:30
作者
Herson, PS [1 ]
Dulock, KA [1 ]
Ashford, MLJ [1 ]
机构
[1] Univ Aberdeen, Inst Med Sci, Dept Biomed Sci, Foresterhill AB25 2ZD, Aberdeen, Scotland
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1997年 / 505卷 / 01期
基金
英国惠康基金;
关键词
D O I
10.1111/j.1469-7793.1997.065bc.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. Cell-free excised membrane patches were used to examine the properties of a novel nicotinamide-adenine dinucleotide (beta-NAD(+))-activated ion channel in the rat insulin-secreting cell line, CRI-G1. 2. In inside-out recordings, beta-NAD(+) (0.05-1.0 mM) induced the appearance of a channel characterized by extremely slow kinetics, with mean open times in the range of seconds. The estimated EC50 for activation was 114 mu M. Channel activity declined with time (run-down) following activation by beta-NAD(+) in excised patches and this was not prevented by intra cellular application of trypsin. 3. The single channel current-voltage relationship was linear with a conductance of 74 pS in symmetrical NaCl. The channel appears equally permeable to Na+, K+ and Cs+, exhibits an appreciable permeability to Ca2+, Mg2+ and Ba2+, but excludes anions. 4. The channel displays an unusual voltage sensitivity, with an abrupt increase in open-state probability at depolarized voltages. 5. Channel opening, in the presence of beta-NAD(+), required both Ca2+ and Mg2+ to be present at the internal side of the membrane. Activation by Ca2+ required a concentration of at least 10 mu M and was maximal at 0.1 mM. Ba2+ did not substitute fur Ca2+ in inducing channel activity nor did it inhibit activation by Ca2+. Increasing the concentration of intracellular Mg2+ stabilized the open state of NAD(+)-activated channels. 6. The non-selective cation channel reported here differs in its gating and modulatory characteristics from non-selective cation channels described in other tissues. This channel may play a role in the pathophysiological reponses of beta-cells to oxidative stress.
引用
收藏
页码:65 / 76
页数:12
相关论文
共 33 条
  • [11] ACTIVATION OF A CAMP-REGULATED CA2+-SIGNALING PATHWAY IN PANCREATIC BETA-CELLS BY THE INSULINOTROPIC HORMONE GLUCAGON-LIKE PEPTIDE-1
    HOLZ, GG
    LEECH, CA
    HABENER, JF
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (30) : 17749 - 17757
  • [12] MECHANISM OF ACTIVATION OF NONSELECTIVE CATION CHANNELS BY PUTATIVE M(4) MUSCARINIC RECEPTOR IN GUINEA-PIG CHROMAFFIN CELLS
    INOUE, M
    IMANAGA, I
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1995, 114 (02) : 419 - 427
  • [13] ATP-SENSITIVE K+-CHANNEL RUN-DOWN IS MG2+ DEPENDENT
    KOZLOWSKI, RZ
    ASHFORD, MLJ
    [J]. PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES, 1990, 240 (1298): : 397 - 410
  • [14] MG2+-DEPENDENT INHIBITION OF K-ATP BY SULFONYLUREAS IN CRI-G1 INSULIN-SECRETING CELLS
    LEE, K
    OZANNE, SE
    HALES, CN
    ASHFORD, MLJ
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1994, 111 (02) : 632 - 640
  • [15] LEE K, 1994, MOL PHARMACOL, V45, P176
  • [16] NADH AND NAD MODULATES CA2+-ACTIVATED K+ CHANNELS IN SMALL PULMONARY ARTERIAL SMOOTH-MUSCLE CELLS OF THE RABBIT
    LEE, S
    PARK, M
    SO, I
    EARM, YE
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1994, 427 (3-4): : 378 - 380
  • [17] ION-CONCENTRATION DEPENDENCE OF THE REVERSAL POTENTIAL AND THE SINGLE CHANNEL CONDUCTANCE OF ION CHANNELS AT THE FROG NEUROMUSCULAR-JUNCTION
    LEWIS, CA
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1979, 286 (JAN): : 417 - 445
  • [18] MICRODOMAINS OF HIGH CALCIUM-CONCENTRATION IN A PRESYNAPTIC TERMINAL
    LLINAS, R
    SUGIMORI, M
    SILVER, RB
    [J]. SCIENCE, 1992, 256 (5057) : 677 - 679
  • [19] MATSCHINSKY FM, 1986, J BIOL CHEM, V261, P14057
  • [20] THE EFFECT OF INTRACELLULAR ANIONS ON ATP-DEPENDENT POTASSIUM CHANNELS OF RAT SKELETAL-MUSCLE
    MCKILLEN, HC
    DAVIES, NW
    STANFIELD, PR
    STANDEN, NB
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1994, 479 (03): : 341 - 351