Protein Kinase G Inhibits T‐type Ca2+ Channels in Rat Cerebral Arteries

Abstract

In rat cerebral arteries, T‐type Ca2+ channels are suppressed by protein kinase A (PKA) signaling. In this study, we examine whether protein kinase G (PKG), another key vasodilatory pathway, exerts a similar or distinctive influence on this conductance. Using patch clamp electrophysiology and cerebral arterial smooth muscle cells from rat, we monitored an inward Ba2+ current that was divisible into nifedipine‐sensitive and –insensitive components. The nifedipine‐insensitive conductance displayed properties reminiscent of T‐type Ca2+ channels; faster activation and steady state inactivation particularly at hyperpolarized potentials. Intriguingly, agents that target key PKG signaling proteins altered T‐type Ca2+ channel activity. In particular, activators of PKG signaling (db‐cGMP, Na nitroprusside, SNAP) suppressed T‐type currents and evoked a hyperpolarized shift in steady state inactivation. PKG inhibitors (KT5823, ODQ) masked this suppression while having no effect on basal T‐type activity. In contrast, PKG manipulations had no influence on the nifedipine‐sensitive L‐type conductance. Cumulatively, our findings support the emerging view that T‐type Ca2+ channels are a key regulatory target of vasodilatory signaling pathways (i.e. PKG and PKA).