Heteromultimeric Kv2.1/9.3 channels contribute to myogenic control of rat middle cerebral arterial (RMCA) diameter

Abstract

Cerebrovascular smooth muscle contractility plays a crucial role in control of cerebral arterial diameter and, thereby, blood flow regulation. K+ channels contribute to this regulation by controlling smooth muscle membrane potential (Em) and Ca2+ influx. Voltage‐dependent K+ channels containing Kv2 subunits are expressed in vascular smooth muscle, but their precise role and molecular composition have not been defined with certainty. Here, we tested if Kv2 subunits associate with silent subunits (Kv5, 6, 8 or 9) to form heterotetrameric channels that contribute to control of RMCA diameter. Stromatoxin‐1 (STX), a Kv2 channel blocker, caused vasoconstriction between 10 and 100 mmHg. However, the voltage‐activation range of homotetrameric Kv2 channels was positive to −40 mV and could not account for STX‐sensitive channel activity at 10 mmHg (Em < −45 mV). Real‐time PCR revealed predominant expression of Kv2.1 and Kv9.3. Comparison of the kinetic and voltage‐dependent properties of Kv2.1/Kv9.3 current (HEK293 cells) with those of native STX‐sensitive current provided evidence of functional identity. Our data indicate that Kv2.1/9.3‐containing channels play an important role in control of cerebral arterial diameter over a range of intra‐luminal pressure that is distinct from that previously reported for Kv1 and large conductance calcium‐activated K+ channels. (Funded by CIHR MOP‐13505)