Resting Em is Regulated by K Channel Activity

Resting Em is primarily determined by K+ permeability. A typical cell has about 30 times more K+ (~ 140 mM) inside the cell compared to extracellular K+ (~5 mM). Thus, when K+ channels open, it is favorable for K+ to move out of the cell according to its concentration gradient leading to hyperpolarization. There are at least five functionally distinguishable K+ channels found in vascular smooth muscle cells (including PASMC): a) voltage-gated K+ (Kv) channels, b) Ca2+-activated K+ (KCa) channels, c) inward-rectifier K+ (K,R) channels, d) ATP-sensitive K+ (KAXP) channels, and e) tandem pore two domain K+ (KT) channels (43, 61). Em is controlled by a balance of outward currents (e.g., K+ currents, Na+/Ca2+ exchange currents, Na+pump currents) and inward currents (e.g., Na+ currents, Ca2+ currents, CI' currents). In PASMC isolated from humans, rats, canines, and mice, activities of Kv (88, 95, 115), KAXP (16), KCa (75), and KT (29) channels all contribute to the regulation of Em. Under resting conditions, inhibition of Kv channels by 4-aminopyridine (4-AP) causes membrane

depolarization, induces Ca -dependent action potentials, and increases [Ca Jcyl in PASMC (Fig. 3). These results suggest that activity ofKv channels plays an important role in regulating resting Em in PASMC (115).

Figure 3.4-Aminopyridine-sensitive Kv currents are involved in membrane depolarization and regulation of [Ca2+]cyt. A: Representative currents, elicited by depolarizing a human PASMC to test potentials ranging between -60 and +80 mV from a holding potential of -70 mV, before (Control), during (4-AP) and after (Wash) treatment with 5 mM 4-AP. Em (B) and [Ca2+]c), (C) were measured in the current-clamp (7=0) mode and using fluorescence microscopy, respectively, before, during, and after application of 5 mM 4-AP (Reproduced from Refs. 37 and 78).

Figure 3.4-Aminopyridine-sensitive Kv currents are involved in membrane depolarization and regulation of [Ca2+]cyt. A: Representative currents, elicited by depolarizing a human PASMC to test potentials ranging between -60 and +80 mV from a holding potential of -70 mV, before (Control), during (4-AP) and after (Wash) treatment with 5 mM 4-AP. Em (B) and [Ca2+]c), (C) were measured in the current-clamp (7=0) mode and using fluorescence microscopy, respectively, before, during, and after application of 5 mM 4-AP (Reproduced from Refs. 37 and 78).

Was this article helpful?

0 0
Reducing Blood Pressure Naturally

Reducing Blood Pressure Naturally

Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.

Get My Free Ebook


Post a comment