Rankin A C, Sitsapesan R, Kane K A
University Department of Medical Cardiology, Royal Infirmary, Glasgow, UK.
J Mol Cell Cardiol. 1990 Dec;22(12):1371-8. doi: 10.1016/0022-2828(90)90982-8.
A background current induced by isoprenaline, and its modulation by adenosine and ATP, have been studied using the whole cell patch clamp technique in guinea-pig ventricular myocytes. Isoprenaline (1-2000 nM) caused an inward shift of the holding current, in addition to increasing the inward calcium current (ICa). The effect on the background current was maximal earlier than the increase in ICa, but was of shorter duration. The magnitude of the background current was concentration dependent with a EC50 of 8 nM. This current was unaffected by tetrodotoxin 20 microM, Cd 200 microM or verapamil, 10 microM and potassium channel blockade (intracellular Cs, extracellular Cs 20 mM, Ba 2 mM or tetraethylammonium 10 mM). Lowering the chloride content of the electrode solution reduced the magnitude of the background current. The background current was also induced by histamine (1 or 10 microM). Adenosine (10-1000 microM) and and ATP (200 microM) antagonised the isoprenaline induced background current and the increase in ICa. The histamine effects on these currents were also reduced by adenosine. These results suggest that this background current may be carried by chloride ions and may be mediated via an increase in intracellular cyclic AMP concentration. Antagonism of this current may contribute to the antiarrhythmic actions of adenosine and ATP but their mechanisms of action are yet to be determined.
采用全细胞膜片钳技术，在豚鼠心室肌细胞中研究了异丙肾上腺素诱导的背景电流及其受腺苷和ATP的调节作用。异丙肾上腺素（1 - 2000 nM）除了增加内向钙电流（ICa）外，还引起了钳制电流的内向偏移。对背景电流的影响比ICa增加出现得更早，但持续时间更短。背景电流的大小呈浓度依赖性，EC50为8 nM。该电流不受20 μM河豚毒素、200 μM镉或10 μM维拉帕米以及钾通道阻断剂（细胞内铯、细胞外20 mM铯、2 mM钡或10 mM四乙铵）的影响。降低电极溶液中的氯化物含量可降低背景电流的大小。组胺（1或10 μM）也可诱导背景电流。腺苷（10 - 1000 μM）和ATP（200 μM）可拮抗异丙肾上腺素诱导的背景电流以及ICa的增加。腺苷也可降低组胺对这些电流的影响。这些结果表明，该背景电流可能由氯离子携带，可能通过细胞内环磷酸腺苷浓度的增加介导。对该电流的拮抗作用可能有助于腺苷和ATP的抗心律失常作用，但其作用机制尚待确定。
