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PKC isozymes differentially regulate BK Ca channels in pulmonary arterial smooth muscle
Author(s) -
Barman Scott A,
White Richard E,
Meadows Mary L,
Zhu Shu
Publication year - 2009
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.23.1_supplement.999.8
Subject(s) - bk channel , protein kinase c , isozyme , pkc alpha , chemistry , smooth muscle , vascular smooth muscle , potassium channel , medicine , signal transduction , endocrinology , microbiology and biotechnology , biology , enzyme , biochemistry
Large conductance, voltage‐ and calcium‐activated potassium (BK Ca ) channel modulation is important in the regulation of pulmonary arterial pressure. Although protein kinases influence BK Ca channel activity in vascular smooth muscle, little is known about the effect of protein kinase C(PKC) on BK Ca channel activity in pulmonary arterial smooth muscle. A novel finding from our laboratory showed that a purified PKC (2nM) catalytic isozyme mixture activated BK Ca channels in pulmonary arterial smooth muscle cells (PASMC) from the Sprague‐Dawley rat (SDR). Based on the presence of western blot expression in SDR PASMC, we assessed the direct effect of specific catalytic PKC isozymes on BK Ca channels in SDR PASMCs using the inside‐out patch configuration. PKC[epsilon](3nM) activated BK Ca channels significantly, but neither PKC[alpha](5nM) nor PKC[delta](8nM) showed any stimulatory effect on BK Ca channels when 100nM Ca 2+ was present. The effect of PKC[alpha] and PKC[delta] on BK Ca channels was also examined when high (100[mu]M) Ca 2+ was present in the inside‐out patches. PKC[alpha] caused short‐term inhibition of channel activity, while PKC[delta] had no inhibitory effect on Ca 2+ ‐mediated BK Ca channel activation. These results suggest that different signaling pathways involving specific PKC isozymes exist in pulmonary arterial smooth muscle to regulate BK Ca channel function. Supported by NIH and AHA.