Findlay Ian
CNRS UMR 6542, Faculté des Sciences, Université de Tours, France.
J Physiol. 2002 Jun 15;541(Pt 3):731-40. doi: 10.1113/jphysiol.2002.019729.
L-type Ca2+ channel currents in native ventricular myocytes inactivate according to voltage- and Ca2+-dependent processes. This study sought to examine the effect of beta-adrenergic stimulation on the contributions of voltage and Ca2+ to Ca2+ current decay. Ventricular myocytes were enzymatically isolated from guinea-pig hearts. Inward whole-cell Cd2+-sensitive L-type Ca2+ channel currents were recorded with the patch clamp technique and comparison was made between inward currents carried by Ca2+ and either Ba2+, Sr2+ or Na+. In control conditions the decay of Ca2+ currents was faster than Ba2+, Sr2+ or Na+ currents at negative voltages while at positive voltages there was no difference. The relationship between voltage and inactivation for Ca2+ currents was bell-shaped, while that for Ba2+, Sr2+, and Na+ currents was sigmoid. Thus depolarisation progressively replaced Ca2+-dependent inactivation in the fast phase of decay of Ca2+ channel currents with rapid voltage-dependent inactivation. In the presence of isoproterenol (isoprenaline) the decay of Ca2+ currents was faster than Ba2+, Sr2+ or Na+ currents at all measured voltages (-40 to +30 mV). The relationship between voltage and inactivation for Ca2+, Ba2+ and Sr2+ currents was bell-shaped, while that for Na+ currents was sigmoid with less inactivation than under control conditions. Therefore the fast phase of decay of Ca2+ channel currents was now almost entirely due to Ca2+. It is concluded that the relative contributions of Ca2+- and voltage-dependent mechanisms of inactivation of L-type Ca2+ channels in native cardiac myocytes are modulated by beta-adrenergic stimulation influencing the amount of rapid voltage-dependent inactivation.
天然心室肌细胞中的L型Ca2+通道电流根据电压和Ca2+依赖性过程而失活。本研究旨在研究β-肾上腺素能刺激对电压和Ca2+对Ca2+电流衰减贡献的影响。从豚鼠心脏中酶解分离出心室肌细胞。采用膜片钳技术记录内向全细胞Cd2+敏感的L型Ca2+通道电流，并比较Ca2+与Ba2+、Sr2+或Na+所携带的内向电流。在对照条件下，在负电压时Ca2+电流的衰减比Ba2+、Sr2+或Na+电流快，而在正电压时则无差异。Ca2+电流的电压与失活之间的关系呈钟形，而Ba2+、Sr2+和Na+电流的关系呈S形。因此，在Ca2+通道电流衰减的快速阶段，去极化逐渐取代了Ca2+依赖性失活，出现了快速的电压依赖性失活。在异丙肾上腺素存在的情况下，在所有测量电压（-40至+30 mV）下，Ca2+电流的衰减比Ba2+、Sr2+或Na+电流快。Ca2+、Ba2+和Sr2+电流的电压与失活之间的关系呈钟形，而Na+电流的关系呈S形，失活程度比对照条件下小。因此，Ca2+通道电流衰减快速阶段现在几乎完全归因于Ca2+。得出的结论是，天然心肌细胞中L型Ca2+通道失活的Ca2+依赖性和电压依赖性机制的相对贡献受到β-肾上腺素能刺激的调节，影响快速电压依赖性失活的量。
