PT - JOURNAL ARTICLE AU - Zhu-Shan Zhang AU - Heng-Jie Cheng AU - Tomohiko Ukai AU - Hideo Tachibana AU - Che-Ping Cheng TI - Enhanced Cardiac L-Type Calcium Current Response to β<sub>2</sub>-Adrenergic Stimulation in Heart Failure DP - 2001 Jul 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 188--196 VI - 298 IP - 1 4099 - http://jpet.aspetjournals.org/content/298/1/188.short 4100 - http://jpet.aspetjournals.org/content/298/1/188.full SO - J Pharmacol Exp Ther2001 Jul 01; 298 AB - The β2-adrenergic receptor (β2-AR)-mediated increase in cardiac L-type Ca2+ current (ICa,L) has been documented in normal subjects. However, the role and mechanism of β2-AR activation on ICa,L in heart failure (HF) are unclear. Accordingly, we compared the effect of zinterol (ZIN), a highly selective β2-AR agonist, on ICa,L in isolated left ventricular cardiomyocytes obtained from normal control and age-matched rats with HF induced by left coronary artery ligation (4 months). ICa,L was measured by using the whole-cell voltage-clamp technique. In normal myocytes, superfusion of ZIN (10−5 M) caused a 21% increase in ICa,L (9.21 ± 0.24 versus 7.59 ± 0.20 pA/pF) (p &lt; 0.05). In HF myocytes, the same concentration of ZIN produced a significantly greater increase (30%) in ICa,L (6.20 ± 0.24 versus 4.75 ± 0.17 pA/pF) (p &lt; 0.01). This ZIN-induced increase in ICa,L was further augmented in both normal and HF myocytes (normal: 59 versus 21%; HF: 71 versus 30%) after the incubation of myocytes with pertussis toxin (PTX, 2 μg/ml, 36°C, 6 h). These effects were not modified by the incubation of myocytes with CGP-20712A (3 × 10−7 M), a β1-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551 (10−7 M), a β2-AR antagonist. In addition, all of the effects induced by ZIN were completely prevented in the presence of an inhibitory cAMP analog, Rp-cAMPS (100 μM, in the patch-pipette solution). In conclusion, β2-AR activation stimulates L-type Ca2+ channels and increases ICa,L in both normal and HF myocytes. In HF, β2-AR activation-induced augmentation of ICa,L was increased. These effects are likely to be mediated through a cAMP-dependent mechanism and coupled with both stimulatory G protein and PTX-sensitive G protein. The American Society for Pharmacology and Experimental Therapeutics