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T‐type Voltage‐gated Ca 2+ Channels Do Not Contribute To The Negative Feedback Regulation Of Myogenic Tone In Murine Superior Epigastric Arteries
Author(s) -
Mullan Brendan,
Pettis Jessica,
Jackson William F
Publication year - 2016
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.30.1_supplement.940.1
Subject(s) - electrical impedance myography , mibefradil , vasoconstriction , vasodilation , constriction , chemistry , myogenic contraction , endocrinology , medicine , anatomy , biophysics , smooth muscle , voltage dependent calcium channel , calcium , biology
T‐type voltage gated Ca 2+ channels (VGCC) have been hypothesized to control spontaneous transient outward currents (STOCs) through large‐conductance Ca 2+ ‐activated K + channels (BK Ca ) and contribute to the negative‐feedback regulation of myogenic tone. We tested this hypothesis in superior epigastric arteries (SEAs) isolated from male C57BL‐6 mice. SEAs were isolated and enzymatically dissociated to obtain single smooth muscle cells for whole‐cell recording of paxilline‐sensitive (PAX, 1 μM) STOCs at −30 mV, or cannulated and studied by pressure myography (80 cm H 2 O, 37°C). The T‐type blocker Ni 2+ (30 μM) had no effect on STOC amplitude (20.1±1.7 pA vs. 20.6±1.7 pA; n = 12, p > 0.05), but increased STOC frequency (0.79±0.15 Hz vs. 1.21±0.22 Hz; n = 12, p < 0.05). While Ni 2+ produced concentration‐dependent constriction of isolated, pressurized SEAs (logEC 50 = −5.6±0.1; Emax = 40±3% constriction), block of BK Ca with PAX had no effect on vasoconstriction induced by 30 μM Ni 2+ (before PAX = 44±11% constriction vs. in the presence of 1μM PAX = 47±11% constriction; n = 6, p > 0.05). In contrast to Ni 2+ , the non‐selective T‐type blocker, mibefradil, produced vasodilation (logEC 50‐ = −6.9±0.2; Emax = 74±8% dilation), whereas the putative T‐type blocker, ML218, had no significant effect on myogenic tone between 10nM and 10μM (n=6–7, p > 0.05). Our data do not support a role for T‐type VGCC in the negative‐feedback regulation of myogenic tone and suggest that Ni 2+ may constrict murine SEAs by means other than block of T‐type VGCC. Support or Funding Information Supported by PO1‐HL070687 and ASPET‐SURF to B. Mullan