Labedipinedilol-A, a novel calcium channel blocker with alpha/beta-adrenoceptor blockade properties, inhibits L-type calcium channels (LTCCs) in rat cerebrovascular smooth muscle cells (CSMCs). We used conventional whole cell patch-clamp electrophysiology to investigate Ba(2+) currents (I(Ba)) through LTCCs in rat CSMCs enzymatically dissociated from rat cerebral arteries. Labedipinedilol-A (1, 10 microM) reversibly inhibited I(Ba) in a voltage-dependent manner without modifying the I(Ba) current-voltage relationship. The I(Ba) was also abolished by the LTCC blocker nifedipine (1 microM), but enhanced by the LTCC activator Bay K8644 (100 nM). Labedipinedilol-A shifted the steady-state inactivation curve of I(Ba) to more negative potentials. Additionally, labedipinedilol-A had greater inhibitory activity on I(Ba) holding at -40 mV than at -80 mV. This might contribute to labedipinedilol-A's more selective effect on vascular muscles compared to cardiac muscles. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and norepinephrine-enhanced I(Ba) were also inhibited by labedipinedilol-A. Pretreatment with the PKC inhibitor chelerythrine (5 microM) attenuated labedipinedilol-A-mediated I(Ba) inhibition. However, the Rho kinase inhibitor Y-27632 (30 microM) had little effect on labedipinedilol-A inhibition of I(Ba). Labedipinedilol-A inhibition of voltage-dependent LTCCs may be, at least in part, due to its modulation of the PKC pathway.