Regulation of Kv1.3 channels in T lymphocytes by serine/threonine phosphorylation

Voltage-activated Kv 1.3 channels, which are involved in normal functions of human T lymphocytes, contain consensus sites for phosphorylation by PKA, PKC, and CaMKII. Because T-cell functions often depend on second-messenger pathways involving serine/threonine phosphorylation, regulation of Kv 1.3 provides a possible means of modulating cell function. This paper presents a brief review of work from my lab on Kv 1.3 regulation in human T cells by temperature, PKC, PKA and calmodulin-dependent pathways - results that are discussed in light of potential sites for phosphorylation within the Kv 1.3 sequence. Also highlighted are several artefacts that we and others have encountered while studying regulation of this channel, all of which reinforce the caution necessary in interpreting effects of hydrophobic compounds on Kv 1.3 current. Pore-forming antibiotics commonly used to obtain perforated-patch recordings (nystatin, amphotericin B) directly inhibit Kv 1.3 channels, as do several drugs used to activate or inhibit second-messenger pathways (forskolin, trifluoperazine, a synthetic diacylglycerol - 1,2-dioctanoyl-sn-glycerol). Thus, direct actions of such drugs may confound studies of their normal biological roles.