ABSTRACT
The smooth muscle cells (SMCs) of pulmonary arteries are electrically silent (1,2). Under normal conditions they do not fire action potentials, either spontaneously or in response to depolarizing current pulses or many depolarizing drugs. The membrane potential of pulmonary artery SMCs is nevertheless an important factor in the regulation of pulmonary vascular tone. This is illustrated by the well-known vasoconstrictor effect of raising the extracellular Kþ concentration, which depolarizes the cells by suppressing the transmembrane Kþ gradient. Contraction occurs at Kþ concentrations as low as 15mM, which depolarizes pulmonary artery SMCs by around 15mV, and increases with increasing Kþ concentration to a maximum above 50mM Kþ, when the membrane potential is nearly eliminated (13). The contractile effect of potassium requires the presence of extracellular Ca2þ, indicating that it depends on Ca2þ influx. Indeed, it is widely recognized that Kþ-induced depolarization causes the opening of voltage-gated Ca2þ channels in the SMC plasma membrane, through which Ca2þ enters the cell to initiate contraction. Perhaps less widely appreciated are studies
suggesting that in smooth muscle the membrane potential can influence additional pathways that regulate the intracellular Ca2þ concentration ([Ca2þ]i). Thus depolarization was found to stimulate the hydrolysis of inositol phospholipids and the synthesis of inositol 1,4,5-trisphosphate (IP3), which triggers the release of Ca2þ from intracellular stores (4,5). This too would raise [Ca2þ]i and promote contraction.Membrane potential may additionally influence the sensitivity of the contractile machinery to Ca2þ (6). The maintenance of a constant negative potential across the plasma membrane of pulmonary artery SMCs therefore helps to maintain [Ca2þ]i at a low level and inhibits cell contraction. This may be important in maintaining the low intrinsic tone that is characteristic of pulmonary arteries in vivo.
