Abstract
Localized control of blood flow and arterial constriction in response to changes in intraluminal pressure are dependent on the intrinsic regulation of smooth muscle cell membrane potential. The melastatin transient receptor potential (TRP) channel TRPM4 is highly selective for monovalent cations, is activated by elevated levels of intracellular Ca2+, and is a critical regulator of smooth muscle membrane depolarization, which serves to open voltage dependent Ca2+channels (VDCC), and resulting in myocyte contraction. Interestingly, Ca2+ activates and inactivates TRPM4, causing the channel to rapidly inactivate under conventional whole‐cell patch clamp conditions. When the slow Ca2+ buffer, ethylene glycol‐bis(2‐aminoethylether)‐N,N,N′,N′‐tetraacetic acid (EGTA), was included in the pipette solution, we identified a transient tetraethylammonium (TEA)‐insensitive inward Na+ current in freshly isolated cerebral arterial myocytes. siRNA‐mediated silencing of TRPM4 and the recently described TRPM4 inhibitor, 9‐phenanthrol, both diminish the open probability (NPo) compared to controls, strongly suggesting the molecular identity of the channel to be TRPM4. This study demonstrates a practical method to record sustained TRPM4 activity and allows for further investigation into mechanisms of channel regulation. AHA0535226N; F31HL094145‐01.
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