Electrophysiologically distinct smooth muscle cell subtypes in rat conduit and resistance pulmonary arteries.
Pulmonary arteries (PAs), particularly those of the rat, demonstrate a prominent voltage-gated K+ (Kv) current (I(Kv)), which plays an important role in the regulation of the resting potential. No detailed characterization of electrophysiological and pharmacological properties of I(Kv), particularly in resistance PA myocytes (PAMs), has been performed. The aim of the present study was therefore to compare I(Kv) in rat conduit and resistance PAMs using the standard patch clamp technique. We found that 67% of conduit PAMs demonstrated a large, rapidly activating I(Kv) which was potently blocked by 4-aminopyridine (4-AP; IC50, 232 microM), but was almost insensitive to TEA (18% block at 20 mM). Thirty-three percent of cells exhibited a smaller, more slowly activating I(Kv) which was TEA sensitive (IC50, 2.6 mM) but relatively insensitive to 4-AP (37% block at 20 mM). These currents (termed I(Kv1) and I(Kv2), respectively) inactivated over different ranges of potential (V(0.5) = -20.2 vs. -39.1 mV, respectively). All resistance PAMs demonstrated a large, rapidly activating and TEA-insensitive K+ current resembling I(Kv1) (termed I(KvR)), but differing significantly from it with respect to 4-AP sensitivity (IC50, 352 microM), activation rate, and inactivation potential range (V(0.5), -27.4 mV). Thus, cells from conduit PAMs fall into two populations with respect to functional I(Kv) expression, while resistance arteries uniformly demonstrate a third type of I(Kv). Comparison of the properties of the native I(Kv) with those of cloned Kv channel currents suggest that I(Kv1) and I(KvR) are likely to be mediated by Kv1.5-containing homo/heteromultimers, while I(Kv2) involves a Kv2.1 alpha-subunit.
Smirnov
Sergey V
SV
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, London SE1 1UL, UK. s.v.smirnov@bath.ac.uk
Beck
Richard
R
Tammaro
Paolo
P
Ishii
Tetsuro
T
Aaronson
Philip I
PI
D000818:Animals; D004546:Elapid Venoms / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance
D004546:Elapid Venoms; D009498:Neurotoxins; D024642:Potassium Channels, Voltage-Gated; C020273:dendrotoxin