High voltage activated, nifedipine‐sensitive and insensitive calcium channels are present in rat cerebral arteries

Whilst L‐type voltage dependent calcium channels (VDCCs) are reported to mediate cerebral vasoconstriction, selective antagonists are ineffective in treating vasospasm. We therefore investigated the expression and characteristics of VDCC subtypes in adult rat cerebral vessels. Quantitative PCR revealed expression of seven subtypes, with the T‐type, Ca V 3.1, and L‐type, Ca V 1.2, channels the most highly expressed. Immunohistochemistry confirmed protein expression for both channels. Isolated smooth muscle cells (holding potential ‐70 or ‐100mV) displayed inward currents that were activated at ‐40mV and maximal at 0‐10mV (10mM BaCl 2 as charge carrier). The current at +10mV had an activation constant (t act ) of 1.92 ±0.02ms and two inactivation constants (t inact ) of 68.9±15.5ms and >300ms. No additional current was found when cells were held at ‐100mV. Nifedipine (1μΜ reduced the peak current in a non‐time dependent fashion, revealing a nifedipine‐insensitive component, that activated and inactivated significantly faster (t act = 1.11±0.06ms; t inact = 23.5±5.6ms). and was abolished by the further addition of the putative T‐type channel blocker mibefradil. When applied singly, either mibefradil (1μM) or NNC‐55 0396 (1μM) abolished all evoked current. We conclude that a nifedipine‐insensitive VDCC with high voltage activation contributes to calcium influx in cerebral arteries in addition to Ca V 1.2.