EXTRACELLULAR DIVALENT AND TRIVALENT CATION EFFECTS ON SODIUM CURRENT KINETICS IN SINGLE CANINE CARDIAC PURKINJE-CELLS
EXTRACELLULAR DIVALENT AND TRIVALENT CATION EFFECTS ON SODIUM CURRENT KINETICS IN SINGLE CANINE CARDIAC PURKINJE-CELLS
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DOI：
10.1113/jphysiol.1992.sp019264
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发表时间：
1992-08-01
影响因子：
5.5
通讯作者：
SHEETS, MF
中科院分区：
文献类型：
--
作者：
HANCK, DA;SHEETS, MF
1. 在 9-14 摄氏度的电压钳条件下，在酶促分离的单个犬心脏浦肯野细胞中表征了细胞外二价阳离子钡、钙、镉、钴、镁、锰、镍和锌以及三价阳离子镧对宏观钠电流 (I(Na)) 的影响。2。所有二（三）价阳离子都会在电导-电压关系中产生去极化位移。 功效顺序（以在峰值 I(Na) 电导中点产生 5 mV 偏移所需的浓度计算）从最低有效到最高有效为 (mM)：Ca2+ (2.97) 几乎等于 Mg2+ (2.67) 几乎等于 Ba2+ (1.93) > Co2+ (1.02) 几乎等于 Mn2+ (0.88) > Ni2+ (0.54) > La3+ (0.095) 几乎等于 Cd2+ (0.083) 几乎等于 Zn2+ (0.076).3。添加二（三）价阳离子也会产生电压依赖性可用性的去极化变化。 功效从最低到最有效的顺序为（mM）：Cd2+（7.70）几乎等于Mg2+（6.86）几乎等于Ba2+（4.50）> Ca2+（2.47）几乎等于Co2+（1.87）几乎等于Mn2+（1.24）几乎等于Ni2+（1.20）> Zn2+ (0.300) > La3+ (0.060).4.Gouy-Chapman-Stern 方程用于评估二（三）价阳离子与表面电荷结合的功效。 表面电荷密度估计为 0.72 个位点 nm-2，并假设产生最小位移的二价阳离子 Mg2+ 被筛选但不与表面电荷结合。 根据电压依赖性可用性，K(D) 从最低到最高亲和力为 (mM)：Ba2+ (2500) > Co2+ (1670) 几乎等于 Mn2+ (1430) 几乎等于 Ca2+ = Cd2+ = Ni2+ (1200) > Zn2+ (250) > La3+ (30).5。所有二（三）价阳离子还产生 I(Na) 尾电流弛豫的浓度依赖性加速。 Ca2+ 和 La3+ 的添加产生了尾电流弛豫的加速，这可以通过根据电压相关可用性的变化预测的表面电荷效应来解释。 Cd2+ 几乎不会对电压相关的可用性产生任何变化，但会显着加速尾电流弛豫。 Zn2+、Ni2+、Mn2+和Co2+也产生了更大的尾电流弛豫加速，这可以通过表面电荷效应来解释。6．二（三）价阳离子以浓度依赖性方式延迟达到峰值 I(Na) 的时间。 达到峰值的时间 I(Na)-电压关系可以通过指数加常数来很好地描述，二（三）价阳离子不会影响斜率因子或常数，但会沿去极化方向移动关系。 与对尾电流的影响类似，添加一些二（三）价阳离子对达到峰值 I(Na) 的时间产生的影响比电压依赖性可用性变化所预期的影响更大。7． I(Na) 的动力学效应是由筛选与表面电荷的结合和电压依赖性阻断引起的。 电压依赖性可用性的变化可能最好地估计二（三）价阳离子的筛选和结合效应。 一些二（三）价阳离子与开放通道的相互作用速率似乎比之前想象的要慢，从而对 I(Na) 的动力学产生影响。
1. The effects of the extracellular divalent cations barium, calcium, cadmium, cobalt, magnesium, manganese, nickel and zinc and the trivalent cation lanthanum on macroscopic sodium current (I(Na)) were characterized in enzymatically isolated single canine cardiac Purkinje cells under voltage clamp at 9-14-degrees-C.2. All di(tri)valent cations produced depolarizing shifts in the conductance-voltage relationship. The order of efficacy, taken as the concentration required to produce a 5 mV shift in the mid-point of peak I(Na) conductance, from least to most effective was (mM): Ca2+ (2.97) almost-equal-to Mg2+ (2.67) almost-equal-to Ba2+ (1.93) > Co2+ (1.02) almost-equal-to Mn2+ (0.88) > Ni2+ (0.54) > La3+ (0.095) almost-equal-to Cd2+ (0.083) almost-equal-to Zn2+ (0.076).3. Addition of di(tri)valent cations also produced depolarizing shifts in voltage-dependent availability. The order of efficacy from the least to most effective was (mM): Cd2+ (7.70) almost-equal-to Mg2+ (6.86) almost-equal-to Ba2+ (4.50) > Ca2+ (2.47) almost-equal-to Co2+ (1.87) almost-equal-to Mn2+ (1.24) almost-equal-to Ni2+ (1.20) > Zn2+ (0.300) > La3+ (0.060).4.The Gouy-Chapman-Stern equations were used to evaluate di(tri)valent cation efficacy in binding to surface charges. Surface charge density was estimated as 0.72 sites nm-2, and it was assumed that Mg2+, the divalent cation that produced the smallest shift, screened but did not bind to surface charges. Based on voltage-dependent availability, K(D) from lowest to highest affinity were (mM): Ba2+ (2500) > Co2+ (1670) almost-equal-to Mn2+ (1430) almost-equal-to Ca2+ = Cd2+ = Ni2+ (1200) > Zn2+ (250) > La3+ (30).5. All di(tri)valent cations also produced a concentration-dependent acceleration of I(Na) tail current relaxation. The addition of Ca2+ and La3+ produced acceleration of tail current relaxations that could be accounted for by the surface charge effects predicted from the shift in voltage-dependent availability. Cd2+, which produced almost no change in voltage-dependent availability, dramatically accelerated tail current relaxation. Zn2+, Ni2+, Mn2+ and Co2+ also produced greater acceleration of tail current relaxation that could be accounted for by surface charge effects.6. Di(tri)valent cations delayed time to peak I(Na) in a concentration-dependent manner. The time to peak I(Na)-voltage relationship was well described by an exponential plus a constant, and di(tri)valent cations did not affect the slope factor or constant but shifted the relationship in the depolarizing direction. Similar to their effect on tail currents, addition of some di(tri)valent cations produced larger effects on time to peak I(Na) than expected from the shift of voltage-dependent availability.7. Kinetic effects on I(Na) result from screening an binding to surface charges and from voltage-dependent block. Shifts in voltage-dependent availability are likely to best estimate the screening and binding effects of di(tri)valent cations. The rates of interactions of some di(tri)valent cations with the open channel appear to be slower than previously thought with resultant effects on the kinetics of I(Na).