Electrophysiologically distinct smooth muscle cell subtypes in rat conduit and resistance pulmonary arteries

Abstract

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 μm), 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 μm), 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 α-subunit.