P2 purinoceptors contribute to ATP-induced inhibition of L-type Ca2+ current in rabbit atrial myocytes

doi:10.1016/S0008-6363(98)00214-4

Cardiovascular Research 1999 41(1):166-174; doi:10.1016/S0008-6363(98)00214-4
© 1999 by European Society of Cardiology

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P₂ purinoceptors contribute to ATP-induced inhibition of L-type Ca²⁺ current in rabbit atrial myocytes

Taku Yamamoto^a, Yoshizumi Habuchi^a^,*, Manabu Nishio^b, Junichiro Morikawa^b and Hideo Tanaka^a

^aDepartment of Laboratory Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan
^bDepartment of Internal Medicine III, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan

^* Corresponding author. Tel.: +81-75-251-5652; fax: +81-75-251-5678; e-mail: yhabuchi@Koto.Kpu-m.ac.jp

Objective: Adenine compounds, including adenosine-5'-triphosphate(ATP) and adenosine (Ado), exert inhibitory effects on myocardiumvia P₁ (subtype A₁) purinoceptors. However, ATP per se is apotent activator of P₂ purinoceptors. Our aim was to elucidatethe respective roles of P₁ and P₂ purinoceptors in the actionsof ATP on L-type calcium current (I_Ca) in rabbit atrial cells.Methods and Results: A whole cell clamp technique was used torecord I_Ca in single atrial cells from the rabbit heart. ATP(0.1 µmol/l–3 mmol/l) produced an inhibitory effecton I_Ca prestimulated by isoproterenol (ISO, 30 nmol/l), evenin the presence of Ado (1 mmol/l). Both 1,3-dipropyl-8-cyclopentylxanthine(A₁ blocker) and suramin (P₂ blocker) partially blocked theATP-induced inhibition of I_Ca, while their co-application nearlycompletely abolished the effect of ATP. ATP- ${gamma}$ S (30 µmol/l)inhibited ISO-stimulated I_Ca significantly, and this inhibitionwas completely blocked by suramin. ${alpha}$ ,β-Methylene-ADP, aninhibitor of hydrolysis of AMP to Ado, eliminated the suramin-resistantcomponent of I_Ca inhibition by ATP. Pretreatment with pertussistoxin (PTX) abolished the ATP inhibition of I_Ca. Both intracellulardialysis with 8Br cAMP and the application of forskolin plus3-isobutyl-1-methylxanthine also eliminated the effect of ATP.Conclusions: Both P₁ and P₂ purinoceptors are involved in theATP inhibition of ISO-stimulated I_Ca in rabbit atrial cells.The P₁ stimulation by ATP results from hydrolysis of ATP toAdo. Both the P₂- and the P₁-mediated effects of ATP and Ado,respectively, involve a PTX-sensitive and cAMP-dependent pathway.

KEYWORDS ATP; L-type calcium current; Purinoceptor; Pertussis toxin; Rabbit; Atrial myocytes

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