MODULATION OF SINGLE HYPERPOLARIZATION-ACTIVATED CHANNELS (I(F)) BY CAMP IN THE RABBIT SINOATRIAL NODE
MODULATION OF SINGLE HYPERPOLARIZATION-ACTIVATED CHANNELS (I(F)) BY CAMP IN THE RABBIT SINOATRIAL NODE
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DOI：
10.1113/jphysiol.1994.sp020038
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发表时间：
1994-02-01
影响因子：
5.5
通讯作者：
MANGONI, M
中科院分区：
文献类型：
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作者：
DIFRANCESCO, D;MANGONI, M
1. 超极化激活的“起搏器”电流（i(f)）被记录在从兔窦房结（SA）细胞膜上切除的内向外贴片上。2. 单通道活动可以在只有几个通道的补丁中解决；单通道尺寸和单通道电导的电压依赖性（0.97 pS）与之前在细胞附着条件下测量的结果相似。3. 在斑块膜的细胞内侧灌注10 μ m cAMP，促进了超极化时单个i(f)通道的打开。camp诱导的i(f)电流激活在没有改变单通道电导的情况下发生。4. 在超极化和含有大量通道的斑块（宏斑块）中，研究了cAMP对通道打开概率的影响。第一潜伏期直方图显示，cAMP将首次打开的概率曲线移动到更短的时间，这与cAMP诱导的通道打开的促进一致。在宏观贴片中，通过慢电压斜坡协议测量打开概率的电压依赖性表明，cAMP在不改变其形状的情况下将概率曲线移动到更正的电压。5. 在无细胞宏贴片中，控制溶液中的归一化开放概率曲线集中在-121.9 mV附近，比附着细胞的宏贴片负电压高约30 mV。斑块切除后曲线的负移只能部分解释为细胞内cAMP的去除，并且在坡道方案中随着时间的推移而进展，表明存在独立于cAMP的损耗过程。
1. The hyperpolarization-activated 'pacemaker' current (i(f)) was recorded in inside-out patches excised from rabbit sino-atrial (SA) node cell membranes. 2. Single-channel activity could be resolved in patches containing only a few channels; the voltage dependence of single-channel size and single-channel conductance (0.97 pS) were similar to those measured previously in cell-attached conditions. 3. Perfusion of the intracellular side of the patch membrane with 10 mu m cAMP facilitated the opening of single i(f) channels on hyperpolarization. The cAMP-induced i(f) current activation occurred without modification of the single-channel conductance. 4. Modification by cAMP of the probability of channel opening was investigated with respect to the latency to first opening during hyperpolarization and in patches containing a large number of channels (macro-patches). First-latency histograms showed that cAMP shifts the probability curve of first openings to shorter times, in agreement with a cAMP-induced facilitation of channel opening. In macro-patches, measurement of the voltage dependence of the open probability by a slow voltage ramp protocol showed that cAMP shifts the probability curve to more positive voltages without modifying its shape. 5. In cell-free macro-patches the normalized open probability curve in control solutions was centred around -121.9 mV, a voltage some 30 mV more negative than in cell-attached macro-patches. Negative shifting of the curve after patch excision could only partly be explained by the removal of intracellular cAMP, and progressed with time during the ramp protocol, suggesting the presence of a run-down process independent from cAMP.