Ca2+ Channel β Subunits Did Not Contribute to the Low Affinity of Cav1.3 to Nifedipine

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Introduction: Ca channel Cav1.3 (α1D subtype) is expressed in many excitable cells as well as Cav1.2 (α1C subtype), and is considered to contribute to pacemaking in nodal cells. Cav1.3 has lower affinity to dihydropyridine Ca antagonits compared to Cav1.2, although the mechanism is not studied well. In this study we evaluated whether co-expression of Ca channel beta subunits might modulate the affinity of Cav1.3 to a Ca antagonist nifedipine. Method: cRNA for Cav1.3 or Cav1.2 were injected to Xenopus oocytes and Ba currents through the expressed channel were measured with two-electrode voltage-clamp method. Blocking effects of nifedipine to the channel subtypes and the modulation of the effect by co-expression of Ca channel β subunits (Cavβ1 or Cavβ2a) were investigated. Result: Nifedipine 10 µM inhibited Cav1.3 by 30±8.5% at holding potential of −100 mV, significantly weaker (p<0.05, n=13) than Cav1.2 by 70±9.8%. Nifedipine showed concentration dependent inhibition to Cav1.3, and blocking action were enhanced at depolarized holding potentials. The IC50 for nifedipine block on both Cav1.3 and Cav1.2 (35.5±16.3 µM and 6.4±3.1 µM at −100 mV) with co-expression of Cavβ2a did not changed significantly, when Cavβ1 were co-expressed instead. Summary: The low affinity of Cav1.3 to nifedipine was confirmed, and the contribution of Cavβ to the low affinity was small.