CaV channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics

<p>The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (CaV) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the CaV channel family are classified according to expression of their pore-forming ��-subunit; moreover, co-expression of accessory ��2��, �� and �� confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. CaV channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several CaV channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of CaV channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that CaV canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of CaV channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.</p>

Performance of downlink massive MIMO in Ricean fading channels with ZF precoder

We investigate the achievable sum rate and energy efficiency of zero-forcing precoded downlink massive multiple-input multiple-output systems in Ricean fading channels. A simple and accurate approximation of the average sum rate is presented, which is valid for a system with arbitrary rank channel means. Based on this expression, the optimal power allocation strategy maximizing the average sum rate is derived. Moreover, considering a general power consumption model, the energy efficiency of the system with rank-1 channel means is characterized. Specifically, the impact of key system parameters, such as the number of users N, the number of BS antennas M, Ricean factor K and the signal-to-noise ratio (SNR) �� are studied, and closed-form expressions for the optimal �� and M maximizing the energy efficiency are derived. Our findings show that the optimal power allocation scheme follows the water filling principle, and it can substantially enhance the average sum rate in the presence of strong line-of-sight effect in the low SNR regime. In addition, we demonstrate that the Ricean factor K has significant impact on the optimal values of M, N and ��.

Achievable sum-rate of multiuser massive MIMO downlink in ricean fading channels

We investigate the achievable ergodic sum-rate of multi-user multiple-input multiple-output systems in Ricean fading channels. We first derive a lower bound on the average signal-to-leakage-and-noise ratio by utilizing the Mullen's inequality, which is then used to analyze the effect of channel mean information on the achievable sum-rate. With these results, a novel statistical-eigenmode space-division multipleaccess downlink transmission scheme is proposed. For this scheme, we derive an exact closed-form expression for the achievable ergodic sum-rate. Our results show that the achievable ergodic sum-rate converges to a saturation value in the high signal-to-noise ratio (SNR) region and reaches to a lower limit value in the lower Ricean K-factor range. In addition, we present tractable upper and lower bounds, which are shown to be tight for any SNR and Ricean K-factor value. Finally, the theoretical analysis is validated via numerical simulations.

Energy efficiency analysis of rank-1 Ricean fading MIMO channels

This paper studies the energy efficiency (EE) of a point-to-point rank-1 Ricean fading multiple-input-multiple-output (MIMO) channel. In particular, a tight lower bound and an asymptotic approximation for the EE of the considered MIMO system are presented, under the assumption that the channel is unknown at the transmitter and perfectly known at the receiver. Moreover, the effects of different system parameters, namely, transmit power, spectral efficiency (SE), and number of transmit and receive antennas, on the EE are analytically investigated. An important observation is that, in the high signal-to-noise ratio regime and with the other system parameters fixed, the optimal transmit power that maximizes the EE increases as the Ricean-K factor increases. On the contrary, the optimal SE and the optimal number of transmit antennas decrease as K increases.

Massive MIMO in sparse channels

Massive multi-user multiple-input multiple-output (MU-MIMO) systems are cellular networks where the base stations (BSs) are equipped with hundreds of antennas, N, and communicate with tens of mobile stations (MSs), K, such that, N ��� K ��� 1. Contrary to most prior works, in this paper, we consider the uplink of a single-cell massive MIMO system operating in sparse channels with limited scattering. This case is of particular importance in most propagation scenarios, where the prevalent Rayleigh fading assumption becomes idealistic. We derive analytical approximations for the achievable rates of maximum-ratio combining (MRC) and zero-forcing (ZF) receivers. Furthermore, we study the asymptotic behavior of the achievable rates for both MRC and ZF receivers, when N and K go to infinity under the condition that N/K ��� c ��� 1. Our results indicate that the achievable rate of MRC receivers reaches an asymptotic saturation limit, whereas the achievable rate of ZF receivers grows logarithmically with the number of MSs.

TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles

<p>Purpose: Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina.</p><p>Methods: Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies. In some experiments, confocal immunolabeling of wholemount preparations was used to examine the localization of specific mechanosensitive TRP channels in retinal vascular smooth muscle cells (VSMCs).</p><p>Results: Reverse transcription-polymerase chain reaction analysis demonstrated mRNA expression for TRPC1, M7, V1, V2, V4, and P1, but not TRPC6 or M4, in isolated retinal arterioles. Immunolabeling revealed plasma membrane, cytosolic and nuclear expression of TRPC1, M7, V1, V2, V4, and P1 in retinal VSMCs. Hypoosmotic stretch-induced Ca2+ influx in retinal VSMCs was reversed by the TRPV2 inhibitor tranilast and the nonselective TRPP1/V2 antagonist amiloride. Inhibitors of TRPC1, M7, V1, and V4 had no effect. Hypoosmotic stretch-activated cation currents were similar in Na+ and Cs+ containing solutions suggesting no contribution by TRPP1 channels. Direct plasma membrane stretch triggered cation current activity that was blocked by tranilast and specific TRPV2 pore-blocking antibodies and mimicked by the TRPV2 activator, ��9-tetrahydrocannabinol. Preincubation of retinal arterioles with TRPV2 blocking antibodies prevented the development of myogenic tone.</p><p>Conclusions: Our results suggest that retinal VSMCs express a range of mechanosensitive TRP channels, but only TRPV2 appears to contribute to myogenic signaling in this vascular bed.</p>