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Protein Kinase G Inhibits T‐type Ca 2+ Channels in Rat Cerebral Arteries
Author(s) -
Harraz Osama F.,
Welsh Donald G.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.921.3
Subject(s) - cgmp dependent protein kinase , nifedipine , protein kinase a , vasodilation , chemistry , patch clamp , cerebral arteries , biophysics , endocrinology , medicine , kinase , microbiology and biotechnology , electrophysiology , biology , biochemistry , calcium , mitogen activated protein kinase kinase
In rat cerebral arteries, T‐type Ca 2+ 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 Ba 2+ current that was divisible into nifedipine‐sensitive and –insensitive components. The nifedipine‐insensitive conductance displayed properties reminiscent of T‐type Ca 2+ channels; faster activation and steady state inactivation particularly at hyperpolarized potentials. Intriguingly, agents that target key PKG signaling proteins altered T‐type Ca 2+ 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 Ca 2+ channels are a key regulatory target of vasodilatory signaling pathways (i.e. PKG and PKA).