Nifedipine Inhibition of High-Voltage Activated Calcium Channel Currents in Cerebral Artery Myocytes Is Influenced by Extracellular Divalent Cations

Figures

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  Figure 1. Nifedipine inhibition of VDCC currents obtained in 10 mM [Ba2+]o ± 100 μM [Ca2+]o. VDCC currents were elicited in rat cerebral artery myocytes in response to successive 10 mV depolarizing voltage steps from a holding potential of −80 mV. (A,B) VDCC currents obtained using 10 mM [Ba2+]o as the charge carrier in nominally Ca2+-free extracellular solution in the absence (A) and presence (B) of nifedipine (1 μM). (C) Summary data demonstrating that ~20 % of VDCC currents using 10 mM [Ba2+]o were not inhibited by 1 μM nifedipine. (D,E) VDCC currents obtained using 10 mM [Ba2+]o plus 100 μM [Ca2+]o in the absence (D) and presence (E) of nifedipine (1 μM). (F) Summary data demonstrating that VDCC currents were completely inhibited by 1 μM nifedipine in 10 mM [Ba2+]o plus 100 μM [Ca2+]o.

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  Figure 2. Properties of VDCC currents obtained using 10 mM [Ba2+]o ± 100 μM [Ca2+]o. (A–C) VDCC currents elicited by depolarizing voltage steps to +10 mV from a holding potential of −80 mV. (A) Effect of increasing concentrations of nifedipine in 10 mM [Ba2+]o. (C) Effect of increasing concentrations of nifedipine in 10 mM [Ba2+]o plus 100 μM [Ca2+]o. Traces in red represent currents obtained in cells prior to the addition of nifedipine. Traces in blue represent current traces obtained in cells following washout of 1 μM nifedipine. (C) Concentration-inhibition curves of nifedipine on VDCC currents obtained in bath solution containing 10 mM [Ba2+]o ± 100 μM [Ca2+]o. (D–F) VDCC currents evoked using a voltage ramp protocol that applied a continuous membrane potential depolarization from −80 to +50 mV over the course of 300 ms. (D) VDCC currents from a cerebral artery myocyte in bath solution containing 10 mM [Ba2+]o. (E) VDCC currents from the same cell depicted in (D) in bath solution containing 10 mM [Ba2+]o plus 100 μM [Ca2+]o. (F) Summary data demonstrating that the membrane potential evoking maximum VDCC current density was not different in bath solution containing 10 mM [Ba2+]o ± 100…

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  Figure 3. Voltage-dependent inactivation and activation characteristics of VDCC currents recorded in 10 mM [Ba2+]o ± 100 μM [Ca2+]o. (A–C) Current recordings obtained from cells using a double-step voltage protocol that applied a 5 s conditioning pulse step to examine steady-state VDCC inactivation. Recordings obtained in extracellular solution containing 10 mM [Ba2+]o (A), 10 mM [Ba2+]o with 1 μM nifedipine (B), and 10 mM [Ba2+]o plus 100 μM [Ca2+]o (C). (D) Steady-state inactivation curves obtained using the voltage protocol illustrated in (A–C). (E) VDCC activation curves derived from currents elicited by successive 10 mV depolarizing voltage steps from a holding potential of −80 mV.

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  Figure 4. Diltiazem abolishes VDCC currents in 10 mM [Ba2+]o ± 100 μM [Ca2+]o. VDCC currents elicited by depolarizing voltage steps to +10 mV from a holding potential of −80 mV in bath solutions containing 10 mM [Ba2+]o (A) or 10 mM [Ba2+]o plus 100 μM [Ca2+]o (B). Traces in red represent currents obtained in cells prior to the addition of diltiazem. Traces in blue represent current traces obtained in cells following washout of 100 μM diltiazem. (C) Concentration-inhibition curves of diltiazem on VDCC currents obtained in extracellular solution containing 10 mM [Ba2+]o ± 100 μM [Ca2+]o.

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  Figure 5. Nifedipine inhibition of VDCC currents obtained in 2 mM [Ba2+]o or 2 mM [Ca2+]o. VDCC currents were elicited in rat cerebral artery myocytes in response to successive 10 mV depolarizing voltage steps from a holding potential of −80 mV. (A,B) VDCC currents obtained using 2 mM [Ba2+]o as the charge carrier in nominally Ca2+-free extracellular solution in the absence (A) and presence (B) of nifedipine (1 μM). (C) Summary data demonstrating that VDCCs currents were completely inhibited by 1 μM nifedipine in bath solution containing 2 mM [Ba2+]o. (D,E) VDCC currents obtained using 2 mM [Ca2+]o in the absence (D) and presence (E) of nifedipine (1 μM). (F) Summary data demonstrating that VDCC currents were completely inhibited by 1 μM nifedipine in bath solution containing 2 mM [Ca2+]o.

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  Figure 6. Concentration-dependent inhibition of VDCC currents by nifedipine in 2 mM [Ba2+]o or 2 mM [Ca2+]o. VDCC currents elicited by depolarizing voltage steps to +10 mV from a holding potential of −80 mV. (A) Effect of increasing concentrations of nifedipine in bath solution containing 2 mM [Ba2+]o. (B) Effect of increasing concentrations of nifedipine in bath solution containing 2 mM [Ca2+]o. Traces in red represent currents obtained in cells prior to the addition of nifedipine. Traces in blue represent current traces obtained in cells following washout of 1 μM nifedipine. (C) Concentration-inhibition curves of nifedipine on VDCC currents obtained in bath solution containing either 2 mM [Ba2+]o or 2 mM [Ca2+]o.