Voltage-gated Na(+) channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B-SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted prote...

We investigate numerically and analytically the coupled dynamics of transmembrane voltage and intracellular calcium cycling in paced cardiac cells using a detailed physiological model, and its reduction to a three-dimensional discrete map. The results provide a theoretical framework to interpret various experimentally observed modes of instability ranging from electromechanically concordant and...

I on channels provide the most rapid way of communication between the cell interior and the external environment by exploiting the differences in electrolyte composition between the internal and external cellular milieu to transmit electrical and chemical signals (1). Voltage-gated ion channels in particular open and close in response to changes in the membrane electrical potential. Voltage-gat...

Voltage-gated K 1 channels are tetramers with each subunit containing six (S1–S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5–S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1–S4) comprise a domain-like voltage-sensing structure. While the topology of this region...

HERG1 K(+) channels are critical for modulating the duration of the cardiac action potential. The role of hERG1 channels in maintaining electrical stability in the heart derives from their unusual gating properties: slow activation and fast inactivation. HERG1 channel inactivation is intrinsically voltage sensitive and is not coupled to activation in the same way as in the Shaker family of K(+)...

The transmembrane domains of HERG (S1-S3) contain six negative charges: three are conserved in all voltage-gated K channels (D456 and D466 in S2, D501 in S3) and three are unique to the EAG family (D411 in S1, D460 in S2, and D509 in S3). We infer the functional role of these aspartates by studying how substituting them with cysteine, one at a time, affects the channel function. D456C is not fu...