GATING OF L-TYPE CA2+ CHANNELS IN EMBRYONIC CHICK VENTRICLE CELLS - DEPENDENCE ON VOLTAGE, CURRENT AND CHANNEL DENSITY

被引:61
作者
MAZZANTI, M [1 ]
DEFELICE, LJ [1 ]
LIU, YM [1 ]
机构
[1] EMORY UNIV, SCH MED, DEPT ANAT & CELL BIOL, ATLANTA, GA 30322 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 1991年 / 443卷
关键词
D O I
10.1113/jphysiol.1991.sp018835
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. L-type calcium channels in embryonic chick heart ventricle have voltage-dependent, time-variant kinetics when they conduct inward currents carried by 20 mM-Ba2+. Depolarizing the membrane from -20 to 20 mV increases mean open time from 1.4 to 4.2 ms. Mean open time increases monotonically with voltage. The single-channel conductance, 18 +/- 2 pS, is approximately linear over this voltage range, and the extrapolated reversal potential is 38 +/- 5 mV. 2. In cell-attached patches with five or more L-type Ca2+ channels in the patch, the currents elicited by 500 ms depolarizing steps, from a -80 mV holding potential, inactivate rapidly and have large tail currents. In the same patch, currents from a -40 mV holding potential are smaller, inactivate more slowly, and have practically no tail currents. 3. In cell-attached patches containing one of two L-type Ca2+ channels, currents from -80 or -40 mV are virtually identical, and they are similar to the currents from multichannel patches held at -40 mV. 4. The voltage-dependent, time-variant kinetics of individual L-type Ca2+ channels are unaltered if the patch is removed from the cell and forms an inside-out configuration. In these experiments the internal membrane was bathed with an artificial, intracellular-like solution containing no phosphorylating enzymes or substrates. 5. Cells bathed in 20 mM-Ba2+ solutions and held at -80 mV have currents with an early phase that inactivates in tens of milliseconds, a late phase that inactivates in hundreds of milliseconds, and a large, slow tail current. Currents from -40 mV have only the late phase and practically no tails. However, if the maximum current is less than 0.1 pA pF-1, records from either -80 or -40 mV are virtually identical, and they are similar to currents from cells with higher channel density held at -40 mV. Furthermore, if cells are stimulated before full recovery from inactivation, the reduced current is accompanied by slower inactivation. 6. Whole-cell currents in 1.5 mM-Ca2+ solutions are entirely abolished by addition of 20-mu-M-nifedipine, and they are enhanced 2-3 times by addition of 30-mu-M-cyclic AMP and 3 mM-ATP to the whole-cell recording electrode. The whole-cell currents in 20 mM-Ba2+ solutions are also completely blocked by 20-mu-M-nifedipine, regardless of kinetics or holding potential. Thus, by definition, the cells we are studying contain only L-type channels. 7. A model of L-type Ca2+ channels that accounts for the essential features of these data includes a voltage-dependent inactivated state and a current-dependent blocked state. The probability that a channel is in the blocked state is proportional to the number of ions that pass through it less the number that leak away. The model assumes that ions crossing a particular channel may block adjacent pores. Such a mechanism explains the rapid 'inactivation' kinetics of L-type Ca2+ currents that develop if channel density is sufficiently high.
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页码:307 / 334
页数:28
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